Ammonia → Nelfinavir

HRID 346872Notes

Reaction equation

HRID 346872 reaction equation
N.[C:2]([NH:6][C:7]([C@@H:9]1[CH2:18][C@H:17]2[C@H:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[CH2:11][N:10]1[CH2:19][C@@H:20]([OH:44])[C@@H:21]([NH:30][C:31](=[O:43])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([O:38]C(=O)C)[C:33]=1[CH3:42])[CH2:22][S:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:8])([CH3:5])([CH3:4])[CH3:3]>CO>[C:2]([NH:6][C:7]([C@@H:9]1[CH2:18][C@H:17]2[C@H:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[CH2:11][N:10]1[CH2:19][C@@H:20]([OH:44])[C@@H:21]([NH:30][C:31](=[O:43])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([OH:38])[C:33]=1[CH3:42])[CH2:22][S:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:8])([CH3:5])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 15433299HCID 15433299, compound

Product 1

HCID 64143NelfinavirYield 54%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Aqueous ammonia (28%, 24 ml) was added to a solution of (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) in methanol (96 ml). The resulting mixture was stirred for 1.5 hours at room temperature. 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 vacuum to give (3S, 4aS, 8aS)-2-[(2R, 3R)-2-hydroxy-3-(3-hydroxy-2-methylbenzoylamino)-4-phenylthiobutyl]decahydroisoquinoline-3-carboxylic acid t-butylamide 17, 8.00 g, as colorless crystals (54% yield from (2R, 3R-benzyloxycarbonylamino-4-phenylthio-2-methanesulfonyloxy-1-(4-nitrobenzoyloxy) butane). 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, 3.5 Hz, 1H), 3.37 (m, 1H), 3.04 (dd, J=8.7, 1.7 Hz, 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 vacuum

Sources & evidence

ORD record
ord-fc507fa148d34c72a0c95f91b0908934
Source dataset
uspto-grants-2007_02
Patent number
US07173059B2

Reaction notes

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