e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Tetrahedron letters

Practical synthesis of an orally active renin inhibitor aliskiren

H Dong, ZL Zhang, JH Huang, R Ma, SH Chen, G Li

Index: Tetrahedron Letters, , vol. 46, # 37 p. 6337 - 6340

Full Text: HTML

Citation Number: 40

Abstract

... Tetrahedron Letters. Volume 46, Issue 37, 12 September 2005, Pages 6337–6340. ... 12 In this letter, we report a convergent synthetic approach featuring Segment AB as the key intermediate, which was envisioned to be derived from the coupling of Segment B (via its Grignard ...

(R)-3-(3-Methylbutanoyl)-4-benzyloxazolidin-2-one Structure

(R)-3-(3-Methyl...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene Structure

4-(bromomethyl)...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

[4-methoxy-3-(3-methoxypropoxy)phenyl]methanol Structure

[4-methoxy-3-(3...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one Structure

(4R)-3-{(2R)-2-...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

Aliskiren inter-9 Structure

Aliskiren inter-9

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

Isovanillin Structure

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

(R)-3-(3-Methylbutanoyl)-4-benzyloxazolidin-2-one Structure

(R)-3-(3-Methyl...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

4-Methoxy-3-(3-methoxypropoxy)benzaldehyde Structure

4-Methoxy-3-(3-...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYL-BUTYRICACID Structure

(R)-2-[3-(3-MET...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene Structure

4-(bromomethyl)...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

[4-methoxy-3-(3-methoxypropoxy)phenyl]methanol Structure

[4-methoxy-3-(3...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

ethyl (2S,4S)-2-amino-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methylhexanoate Structure

ethyl (2S,4S)-2...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

ethyl (αS,γS)-α-{[(1,1-dimethylethoxy)carbonyl]amino}-4-methoxy-3-(3-methoxypropoxy)-γ-(1-methylethyl)benzenepentanoate Structure

ethyl (αS,γS)-α...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one Structure

(4R)-3-{(2R)-2-...

~%

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

Isovanillin Structure

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

4-Methoxy-3-(3-methoxypropoxy)benzaldehyde Structure

4-Methoxy-3-(3-...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYL-BUTYRICACID Structure

(R)-2-[3-(3-MET...

~%

Aliskiren inter-9 Structure

Aliskiren inter-9

4-Methoxy-3-(3-methoxypropoxy)benzaldehyde Structure

4-Methoxy-3-(3-...

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene Structure

4-(bromomethyl)...

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

[4-methoxy-3-(3-methoxypropoxy)phenyl]methanol Structure

[4-methoxy-3-(3...

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYL-BUTYRICACID Structure

(R)-2-[3-(3-MET...

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

Isovanillin Structure

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one Structure

(4R)-3-{(2R)-2-...

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

(R)-3-(3-Methylbutanoyl)-4-benzyloxazolidin-2-one Structure

(R)-3-(3-Methyl...

~%

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

Benzyl chloromethyl ether Structure

Benzyl chlorome...

~%

1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene Structure

1-(((S)-2-(Brom...

(R)-3-(3-Methylbutanoyl)-4-benzyloxazolidin-2-one Structure

(R)-3-(3-Methyl...

~%

1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene Structure

1-(((S)-2-(Brom...

Aliskiren inter-10 Structure

Aliskiren inter-10

~%

1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene Structure

1-(((S)-2-(Brom...

(2S)-3-methyl-2-[(phenylmethoxy)methyl]butanoic acid Structure

(2S)-3-methyl-2...

~%

1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene Structure

1-(((S)-2-(Brom...

Benzyl alcohol Structure

~%

1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene Structure

1-(((S)-2-(Brom...

Aliskiren inter-9 Structure

Aliskiren inter-9

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

Isovanillin Structure

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

(R)-3-(3-Methylbutanoyl)-4-benzyloxazolidin-2-one Structure

(R)-3-(3-Methyl...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

4-Methoxy-3-(3-methoxypropoxy)benzaldehyde Structure

4-Methoxy-3-(3-...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYL-BUTYRICACID Structure

(R)-2-[3-(3-MET...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene Structure

4-(bromomethyl)...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

[4-methoxy-3-(3-methoxypropoxy)phenyl]methanol Structure

[4-methoxy-3-(3...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

ethyl (2S,4S)-2-amino-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methylhexanoate Structure

ethyl (2S,4S)-2...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

ethyl (αS,γS)-α-{[(1,1-dimethylethoxy)carbonyl]amino}-4-methoxy-3-(3-methoxypropoxy)-γ-(1-methylethyl)benzenepentanoate Structure

ethyl (αS,γS)-α...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one Structure

(4R)-3-{(2R)-2-...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

Benzenepentanoic acid, α-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methoxy-3-(3-methoxypropoxy)-γ-(1-methylethyl)-, (αS,γS) Structure

Benzenepentanoi...

N,O-Dimethylhydroxylamine hydrochloride Structure

N,O-Dimethylhyd...

~%

tert-butyl N-[(2S,4S)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-1-[methoxy(methyl)amino]-5-methyl-1-oxohexan-2-yl]carbamate Structure

tert-butyl N-[(...

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

~%

Aliskiren Structure

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYL-BUTYRICACID Structure

(R)-2-[3-(3-MET...

~%

Aliskiren Structure

2-cyano-2-methyl-propanamide Structure

2-cyano-2-methy...

~%

Aliskiren Structure

4-Methoxy-3-(3-methoxypropoxy)benzaldehyde Structure

4-Methoxy-3-(3-...

~%

Aliskiren Structure

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene Structure

4-(bromomethyl)...

~%

Aliskiren Structure

[4-methoxy-3-(3-methoxypropoxy)phenyl]methanol Structure

[4-methoxy-3-(3...

~%

Aliskiren Structure

tert-Butyl ((1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-4-methylpentyl)carbamate Structure

tert-Butyl ((1S...

~%

Aliskiren Structure

3N-Benzyloxycarbonyl 3-Amino-2,2-dimethylpropanamide Structure

3N-Benzyloxycar...

~%

Aliskiren Structure

tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate Structure

tert-Butyl ((2S...

~%

Aliskiren Structure

Aliskiren inter-9 Structure

Aliskiren inter-9

~%

Aliskiren Structure

Isovanillin Structure

~%

Aliskiren Structure

Aliskiren inter-10 Structure

Aliskiren inter-10

~%

Aliskiren Structure

1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene Structure

1-(((S)-2-(Brom...

~%

Aliskiren Structure

(2S)-3-methyl-2-[(phenylmethoxy)methyl]butanoic acid Structure

(2S)-3-methyl-2...

~%

Aliskiren Structure

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene) Structure

2-(3-Methoxypro...

~%

Aliskiren Structure

ethyl (2S,4S)-2-amino-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methylhexanoate Structure

ethyl (2S,4S)-2...

~%

Aliskiren Structure

tert-butyl N-[1-hydroxy-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-5-methylhexan-2-yl]carbamate Structure

tert-butyl N-[1...

~%

Aliskiren Structure

ethyl (αS,γS)-α-{[(1,1-dimethylethoxy)carbonyl]amino}-4-methoxy-3-(3-methoxypropoxy)-γ-(1-methylethyl)benzenepentanoate Structure

ethyl (αS,γS)-α...

~%

Aliskiren Structure

(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one Structure

(4R)-3-{(2R)-2-...

~%

Aliskiren Structure

((1S,2S,4S)-2-hydroxy-4-hydroxymethyl-1-((S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl)-5-methyl-hexyl)-carbamic acid tert-butyl ester Structure

((1S,2S,4S)-2-h...

~%

Aliskiren Structure

3-Amino-2,2-dimethylpropanamide Structure

3-Amino-2,2-dim...

~%

Aliskiren Structure

Benzyl alcohol Structure

~%

Aliskiren inter-10 Structure

Aliskiren inter-10

(S)-2-Benzyloxymethyl-3-methylbutan-1-ol Structure

(S)-2-Benzyloxy...

~%

Aliskiren Structure

4-Methoxy-3-(3-methoxypropoxy)benzaldehyde Structure

4-Methoxy-3-(3-...

~%

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

[4-methoxy-3-(3-methoxypropoxy)phenyl]methanol Structure

[4-methoxy-3-(3...

~%

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)benzene Structure

4-(bromomethyl)...

~%

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

Isovanillin Structure

~%

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

(R)-3-(3-Methylbutanoyl)-4-benzyloxazolidin-2-one Structure

(R)-3-(3-Methyl...

~%

(R)-2-[3-(3-METHOXYPROPOXY)-4-METHOXYBENZYL]-3-METHYLBUTAN-1-OL Structure

(R)-2-[3-(3-MET...

Practical synthesis of an orally active renin inhibitor alis...

[Dong, Hua; Zhang, Zhi-Liu; Huang, Jia-Hui; Ma, Rujian; Chen, Shu-Hui; Li, Ge Tetrahedron Letters, 2005 , vol. 46, # 37 p. 6337 - 6340]