Diisopropylethylamine → 4-diphenylcarbamoyl-1-pentyl(phenyl)carbamoyl-(2S)-hexahydro-2-pyrazinecarboxylic acid

HRID 2226599Notes

Reaction equation

C(O)(=O)C.[C:5]1([N:11]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:12]([N:14]2[CH2:19][CH2:18][NH:17][C@H:16]([C:20]([OH:22])=[O:21])[CH2:15]2)=[O:13])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)C(C)C)(C)C.[CH2:38]([N:43]([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:44](Cl)=[O:45])[CH2:39][CH2:40][CH2:41][CH3:42]>CN(C=O)C>[CH2:38]([N:43]([C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[C:44]([N:17]1[CH2:18][CH2:19][N:14]([C:12](=[O:13])[N:11]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:15][C@H:16]1[C:20]([OH:22])=[O:21])=[O:45])[CH2:39][CH2:40][CH2:41][CH3:42]

Participants

Conditions

Temperature: 25 °C

Procedure

A stirred solution of 0.383 g (1.00 mmole) of (S)-4-(diphenylcarbamoyl)piperazine-2-carboxylic acid acetate salt (from Step C) and 0.400 g (3.09 mmole) of N,N-diisopropylethylamine in 6 ml of DMF at 0° C. was treated with 0.253 g (1.12 mmole) of N-pentyl-N-phenylcarbamoyl chloride (from Step B) and then was warmed to 25° C. for 16 hours. The DMF was removed in vacuo and the residue was partitioned between 20 ml of 1N HCl and 50 ml of chloroform which was dried over sodium sulfate and concentrated in vacuo to a yellow oil. The oil was flash chromatographed over 100 cc of silica gel with 12×25 ml of chloroform, 10×25 ml of 80:20:2 chloroform-methanol-ammonia water. Fractions 19-26 were combined and concentrated to 0.338 g (ammonium salt) of clear glass which was homogeneous by TLC (80:20:2 chloroform-methanol-ammonia water, Rf =0.4). The product was partitioned between 20 ml. of 1N HCl and 30 ml of chloroform which was dried over sodium sulfate and concentrated in vacuo to 0.337 g (72%) of a clear glass.

Workup

customThe DMF was removed in vacuo
customthe residue was partitioned between 20 ml of 1N HCl and 50 ml of chloroform which
dry with materialwas dried over sodium sulfate
concentrationconcentrated in vacuo to a yellow oil
customchromatographed over 100 cc of silica gel with 12×25 ml of chloroform, 10×25 ml of 80:20:2 chloroform-methanol-ammonia water
concentrationconcentrated to 0.338 g (ammonium salt) of clear glass which
customThe product was partitioned between 20 ml
dry with materialof 1N HCl and 30 ml of chloroform which was dried over sodium sulfate
concentrationconcentrated in vacuo to 0.337 g (72%) of a clear glass

Sources & evidence

ORD record: ord-8d0ff148d0db408ab0d307aab131ee38
Source dataset: uspto-grants-1994_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05348955

Reaction notes

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