tert-Butyl 3-(4-amino-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate → tert-Butyl 3-(4-(4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate

HRID 592395Notes

Reaction equation

HRID 592395 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[N:26][N:27]([CH:29]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30]2)[CH:28]=1>CO.O>[C:19]([C:16]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:6]2[C:5]([Cl:22])=[CH:4][N:3]=[C:2]([NH:23][C:24]3[CH:25]=[N:26][N:27]([CH:29]4[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30]4)[CH:28]=3)[N:7]=2)[CH2:18][CH2:17]1)(=[O:20])[NH2:21]

Participants

5

Reactant 2

HCID 46738147tert-Butyl 3-(4-amino-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate2×HCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 86712302tert-Butyl 3-(4-(4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A stirred solution of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.150 g, 0.446 mmol), 4-amino-1-(1-Boc-pyrrolidin-3-yl)-1H-pyrazole (0.225 g, 0.892 mmol) in MeOH (10 mL) and water (1.0 mL) was heated at 70° C. for 2 days. Additional 4-amino-1-(1-boc-pyrrolidin-3-yl)-1H-pyrazole (0.125 g, 0.446 mmol) was added and the mixture was heated for a further 16 hours at reflux. After cooling the solvent was removed to afford a crude red oil which was purified by silica gel column chromatography (0-100% EtOAc in cyclohexane) to give the title compound A21 as a red oil (0.164 g, 67% yield). LCMS-C: rt 5.51 min; m/z 551.9 [M+H]+.

Workup

  1. temperaturethe mixture was heated for a further 16 hours
  2. temperatureat reflux
  3. temperatureAfter cooling the solvent
  4. customwas removed
  5. customto afford a crude red oil which
  6. customwas purified by silica gel column chromatography (0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-1d2b7b3e07064de68ea903f5c491d012
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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