((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride → {(R)-3-[(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl ester

HRID 72169Notes

Reaction equation

HRID 72169 reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C@H:17]([C:21]([OH:23])=O)[CH:18]([CH3:20])[CH3:19].Cl.[CH2:25]([O:32][P:33]([CH2:42][C@H:43]([OH:46])[CH2:44][NH2:45])([CH2:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH2:25]([O:32][P:33]([CH2:42][C@H:43]([OH:46])[CH2:44][NH:45][C:21](=[O:23])[C@@H:17]([NH:16][C:13](=[O:15])[C@@H:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH:10]([CH3:11])[CH3:12])[CH:18]([CH3:20])[CH3:19])([CH2:35][CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)=[O:34])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

3

Reactant 2

HCID 68622110((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochlorideHCID 131729735HCID 131729735, compound

Product 1

HCID 68620254{(R)-3-[(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl ester

Procedure

The title compound was prepared substantially in a similar manner as Example 12 Method B using N-Boc-L-valine-L-valine and ((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl phosphinic acid benzyl ester hydrochloride. The crude product was purified by gradient flash chromatography (methanol/methylene chloride) on a RediSep disposable column. 1H NMR (CD3Cl, 300 MHz): δ 7.45-7.30 (m, 5H), 6.50 (d, 1H), 5.15-4.98 (m, 3H), 4.55 (br.s, 1H), 4.33-4.22 (m, 1H), 4.20-4.05 (m, 1H), 3.95-3.84 (m, 1H), 3.56-3.40 (m, 1H), 3.38-3.26 (m, 1H), 2.35-2.12 (m, 2H), 1.98-1.79 (m, 4H), 1.78-1.63 (m, 4H), 1.49 (s, 9H), 1.38-1.15 (m, 3H), 1.13-0.85 (m, 14H). 31P NMR (CD3OD, 300 MHz): δ 59.46, 58.33. LCMS m/z: [M+H]+=624.85.

Workup

  1. customThe crude product was purified by gradient flash chromatography (methanol/methylene chloride) on a RediSep disposable column

Sources & evidence

ORD record
ord-564eb6df74794892aa81e7cf13eaea35
Source dataset
uspto-grants-2014_09
Patent number
US08828974B2

Reaction notes

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