Morpholine → ((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-morpholin-4-yl-methanone

HRID 409439Notes

Reaction equation

HRID 409439 reaction equation
[N+](C1C=CC(O[C:11]([N:13]2[CH2:17][C@@H:16]([N:18]([CH2:31][C:32]3[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=3)[C:19]3[N:24]=[CH:23][C:22]([C:25]4[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=4)=[CH:21][N:20]=3)[CH2:15][C@H:14]2[CH2:46][CH3:47])=[O:12])=CC=1)([O-])=O.[NH:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1>>[F:43][C:42]([F:44])([F:45])[C:34]1[CH:33]=[C:32]([CH:37]=[C:36]([C:38]([F:40])([F:41])[F:39])[CH:35]=1)[CH2:31][N:18]([C:19]1[N:24]=[CH:23][C:22]([C:25]2[CH:26]=[N:27][N:28]([CH3:30])[CH:29]=2)=[CH:21][N:20]=1)[C@@H:16]1[CH2:17][N:13]([C:11]([N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)=[O:12])[C@H:14]([CH2:46][CH3:47])[CH2:15]1

Participants

3

Reactant 2

HCID 8083MorpholineHCID 59614333(2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 4-nitro-phenyl ester

Product 1

HCID 42632979((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-morpholin-4-yl-methanoneYield 73.6%

Conditions

Temperature
80 °C

Procedure

A mixture of (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid 4-nitro-phenyl ester (0.1 mmol; 66 mg) and morpholine (1.15 mmol; 1.00 g) is stirred for 20 hours at 80° C. The reaction mixture is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give ((2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-morpholin-4-yl-methanone (45 mg; 73%) %); ESI-MS m/z: 612 [M+1]+, Retention time 2.07 min (condition A).

Workup

  1. customThe reaction mixture is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-aa203a07cb6e4462908b4e5973532deb
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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