N-[(Phenylmethoxy)carbonyl]-L-histidine → {(R)-3-[(S)-2-Amino-3-(lH-imidazol-4-yl)-propionylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid

HRID 72165Notes

Reaction equation

HRID 72165 reaction equation
Cl.C([O:9][P:10]([CH2:19][C@H:20]([OH:23])[CH2:21][NH2:22])([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:11])C1C=CC=CC=1.C1C=CC(COC([NH:34][C@H:35]([C:42](O)=[O:43])[CH2:36][C:37]2[NH:41][CH:40]=[N:39][CH:38]=2)=O)=CC=1>>[NH2:34][C@@H:35]([CH2:36][C:37]1[N:41]=[CH:40][NH:39][CH:38]=1)[C:42]([NH:22][CH2:21][C@@H:20]([OH:23])[CH2:19][P:10]([CH2:12][CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1)(=[O:11])[OH:9])=[O:43]

Participants

3

Reactant 2

HCID 736313N-[(Phenylmethoxy)carbonyl]-L-histidineHCID 68622110((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride

Product 1

HCID 178511790{(R)-3-[(S)-2-Amino-3-(lH-imidazol-4-yl)-propionylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid

Procedure

The title compound was prepared substantially following the procedures as set forth in Step 4, Example 1, Method A, and employing ((R)-3-Amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride and N-Cbz-L-histidine-OH as the starting materials. Subsequent hydrogenation of the resulting product in accordance with the procedures of Step 5, Example 1, Method B, and RP-HPLC purification yielded the title compound. 1H NMR (CD3OD, 300 MHz): δ 8.16 (s, 1H), 7.19 (s, 1H), 4.15 (t, 1H), 4.12-3.98 (m, 1H), 3.38-3.10 (m, 4H), 1.94 (br.d, 2H), 1.85-1.60 (m, 6H), 1.56 (dd, 2H), 1.40-1.16 (m, 3H), 1.15-0.96 (m, 2H). 31P NMR (CD3OD, 300 MHz): δ 41.59. LCMS m/z: [M+H]+=373.2

Workup

  1. customThe title compound was prepared substantially
  2. customSubsequent hydrogenation of the resulting product in accordance with the procedures of Step 5, Example 1, Method B, and RP-HPLC purification

Sources & evidence

ORD record
ord-b4d214f50ba54a1c8fb174af9e3680d6
Source dataset
uspto-grants-2014_09
Patent number
US08828974B2

Reaction notes

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