Benzyloxycarbonyl-asparagine → [(R)-3-((S)2-Amino-3-carbamoyl-propionylamino)-2-hydroxy-propyl]-cyclohexylmethyl-phosphinic acid

HRID 72167Notes

Reaction equation

HRID 72167 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:40](O)=[O:41])[CH2:36][C:37]([NH2:39])=[O:38])=O)=CC=1>>[NH2:34][C@@H:35]([CH2:36][C:37](=[O:38])[NH2:39])[C:40]([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:41]

Participants

3

Reactant 2

HCID 75314Benzyloxycarbonyl-asparagineHCID 68622110((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride

Product 1

HCID 11653179[(R)-3-((S)2-Amino-3-carbamoyl-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-asparagine-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 4.26-4.13 (m, 1H), 4.12-3.98 (m, 1H), 3.42-3.32 (m, 2H), 2.98-2.71 (m, 2H), 1.93 (br.d, 2H), 1.84-1.58 (m, 6H), 1.51 (dd, 2H), 1.42-1.15 (m, 3H), 1.13-0.94 (m, 2H). 31P NMR (CD3OD, 300 MHz): δ 40.16. LCMS m/z: [M+H]+=350.3.

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-ecfe81011e914700930a5eeab8a2a876
Source dataset
uspto-grants-2014_09
Patent number
US08828974B2

Reaction notes

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