Benzyloxycarbonyl-L-proline → Cyclohexylmethyl-{(R)-2-hydroxy-3-[((S)-pyrrolidine-2-carbonyl)-amino]-propyl}-phosphinic acid

HRID 72155Notes

Reaction equation

HRID 72155 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.C([N:34]1[CH2:41][CH2:40][CH2:39][C@H:35]1[C:36](O)=[O:37])(OCC1C=CC=CC=1)=O>>[CH:13]1([CH2:12][P:10]([CH2:19][C@H:20]([OH:23])[CH2:21][NH:22][C:36]([C@@H:35]2[CH2:39][CH2:40][CH2:41][NH:34]2)=[O:37])(=[O:11])[OH:9])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

3

Reactant 2

HCID 101987Benzyloxycarbonyl-L-prolineHCID 68622110((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride

Product 1

HCID 11551696Cyclohexylmethyl-{(R)-2-hydroxy-3-[((S)-pyrrolidine-2-carbonyl)-amino]-propyl}-phosphinic acid

Procedure

Step 4, Method B of Example 1 was substantially repeated in this Example 7 except for employing ((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride and N-Cbz-L-proline as the starting materials. Subsequent hydrogenation of the resulting benzyl ester in accordance with the procedures of Step 5, Method A of Example 1 and RP-HPLC purification yielded the title compound. 1H NMR (CD3OD, 300 MHz): δ 4.32-4.18 (m, 1H), 4.13-3.95 (m, 1H), 3.55-3.20 (m, 4H), 2.52-2.35 (m, 1H), 2.15-1.99 (m, 3H), 1.95 (br. d, 2H), 1.80-1.58 (m, 6H), 1.52 (dd, 2H), 1.40-1.15 (m, 3H), 1.13-0.95 (m, 2H). 31P NMR (CD3OD, 300 MHz): δ 42.01. LCMS m/z: [M+H]+=333.2.

Workup

  1. customSubsequent hydrogenation of the resulting benzyl ester in accordance with the procedures of Step 5, Method A of Example 1 and RP-HPLC purification

Sources & evidence

ORD record
ord-d96d0edd59024db093086e8b6fcc1b12
Source dataset
uspto-grants-2014_09
Patent number
US08828974B2

Reaction notes

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