1-Pyrrolidinamine → HCID 57970128, compound

HRID 1666611Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N+:3]=1[O-].Cl.[NH2:12][C@H:13]1[CH2:17][CH2:16][N:15]([C:18](=[O:31])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=2)[CH2:14]1.NN1CCCC1.[CH3:38][CH:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.C(N(CC)C(C)C)(C)C>C(O)CCC>[CH3:38][CH:39]1[CH2:44][CH2:43][N:42]([C:6]2[CH:5]=[C:4]([CH3:9])[N:3]=[C:2]([NH:12][C@H:13]3[CH2:17][CH2:16][N:15]([C:18](=[O:31])[CH2:19][C:20]4[CH:21]=[CH:22][C:23]([O:26][C:27]([F:28])([F:29])[F:30])=[CH:24][CH:25]=4)[CH2:14]3)[CH:7]=2)[CH2:41][CH2:40]1

Participants

Conditions

Temperature: 110 °C

Procedure

In the same manner as in Example 13 (1), 1-((S)-3-(4-chloro-6-methyl-1-oxypyridin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.64 g) was obtained from 2,4-dichloro-6-methylpyridin-1-oxide (0.50 g) and 1-((S)-3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (1.1 g). (2) A mixture of 1-((S)-3-(4-chloro-6-methyl-1-oxypyridin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (300 mg), 4-methylpiperidine (0.30 g), N,N-diisopropylethylamine (0.40 mL), and n-butanol (0.60 mL) was heated at 110° C. for 15 h. The mixture was cooled to room temperature, then the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate−ethyl acetate/methanol=10:1) to obtain the title compound (40 mg) and 1-((S)-3-(4,6′-dimethyl-1′-oxy-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (200 mg). (3) 1-((S)-3-(4,6′-Dimethyl-1′-oxy-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-2′-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (200 mg) was dissolved in methanol (6 mL), followed by addition of 10% Pd—C (200 mg), and the mixture stirred overnight at 40° C. under hydrogen atmosphere. The catalyst was removed by Celite filtration, then the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol=10:1) to obtain the title compound (64 mg).

Workup

temperatureThe mixture was cooled to room temperature
customthe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate−ethyl acetate/methanol=10:1)

Sources & evidence

ORD record: ord-7ab834c923084f9597ce6439b0571492
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044068B2

Reaction notes

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