Ammonia → Nelfinavir

HRID 636852Notes

Reaction equation

HRID 636852 reaction equation
[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:43])[C@@H:20]([NH:29][C:30](=[O:42])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([O:37]C(=O)C)[C:32]=1[CH3:41])[CH2:21][S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N>CO>[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:43])[C@@H:20]([NH:29][C:30](=[O:42])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([OH:37])[C:32]=1[CH3:41])[CH2:21][S:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 15433299HCID 15433299, compound

Product 1

HCID 64143NelfinavirYield 54%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The obtained (3S, 4aS, 8aS)-2-[(2R, 3R)-3-(3-acetoxy-2-methyl-benzoylamino)-2-hydroxy-4-phenylthiobutyl]decahydroisoquinoline-3-carboxylic acid t-butylamide (12.7 g) was dissolved in methanol (96 ml) and 28% aqueous ammonia (24 ml) was added, which was followed by stirring for 1.5 hours. The resulting precipitate was collected by filtration and washed with a mixed solution of methanol (75 ml)/water (25 ml). The residue was dried at 50° C. under reduced pressure to give (3S, 4aS, 8aS)-2-[(2R, 3R)-2-hydroxy-3-(3-hydroxy-2-methylbenzoylamino)-4-phenylthiobutyl]decahydroisoquinoline-3-carboxylic acid t-butylamide (compound [15], 8.00 g, yield 54%, from (2R, 3R-benzyloxycarbonylamino-4-phenylthio-2-methanesulfonyloxy-1-(4-nitrobenzoyloxy)butane) as colorless crystals. 1H-NMR (CD3OD, 300 MHz) δ: 7.49 (m,2H), 7.27 (m,2H), 7.17 (m,1H), 7.01 (m,1H), 6.90 (m,1H), 6.79 (m,1H), 4.43 (m,1H), 4.06 (m,1H), 3.54 (dd,J=10.1,3.5Hz,1H), 3.37 (m,1H), 3.04 (dd,J=8.7,1.7Hz,1H), 2.60 (m,2H), 2.24 (s,3H), 2.17 (m,2H), 2.01 (m,1H), 1.9-1.1 (m,11H), 1.17 (s,9H)

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. washwashed with a mixed solution of methanol (75 ml)/water (25 ml)
  3. customThe residue was dried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-0bc3f68077ee4d488868a9f16a0acd3c
Source dataset
uspto-grants-2001_02
Patent number
US06194589B1

Reaction notes

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