Hydrochloric Acid → 4-(2,5-dimethyl-4-(4-(5-methyl-1H-pyrazol-3-ylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)cyclohexanone

HRID 2093811Notes

Reaction equation

[CH3:1][C:2]1[CH:8]=[C:7]([CH:9]2[CH2:18][CH2:17][C:12]3([O:16]CCO3)[CH2:11][CH2:10]2)[C:6]([CH3:19])=[CH:5][C:3]=1[NH2:4].Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=2)[C:24]([C:34]([F:37])([F:36])[F:35])=[CH:23][N:22]=1.Cl.CO>CC(O)C>[CH3:19][C:6]1[CH:5]=[C:3]([NH:4][C:21]2[N:26]=[C:25]([NH:27][C:28]3[CH:32]=[C:31]([CH3:33])[NH:30][N:29]=3)[C:24]([C:34]([F:35])([F:37])[F:36])=[CH:23][N:22]=2)[C:2]([CH3:1])=[CH:8][C:7]=1[CH:9]1[CH2:10][CH2:11][C:12](=[O:16])[CH2:17][CH2:18]1

Participants

Conditions

Temperature: 125 °C

Procedure

A mixture of 2,5-dimethyl-4-(1,4-dioxaspiro[4.5]decan-8-yl)aniline (111.3 mg, 0.43 mmol), 2-chloro-N-(5-methyl-1H-pyrazol-3-yl)-5-(trifluoromethyl)pyrimidin-4-amine (119.6 mg, 0.43 mmol), HCl (4 N in water, 0.11 mL, 0.43 mmol) in i-PrOH (4.0 mL) was heated at 125° C. in an oil bath over night. The reaction mixture was concentrated in vacuo. The crude product was dissolved in THF (2 mL), MeOH (1 mL) and HCl (4N in water, 0.11 mL, 0.43 mmol), and stirred at room temperature for 2 h. The reaction mixture was concentrated in vacuo, followed by purification by silica chromatography (0-100% EtOAc in hexanes gradient) to afford 4-(2,5-dimethyl-4-(4-(5-methyl-1H-pyrazol-3-ylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)cyclohexanone; ESMS m/z 459.2 (M+H+).

Workup

concentrationThe reaction mixture was concentrated in vacuo
dissolutionThe crude product was dissolved in THF (2 mL)
concentrationThe reaction mixture was concentrated in vacuo
customfollowed by purification by silica chromatography (0-100% EtOAc in hexanes gradient)

Sources & evidence

ORD record: ord-730738e9685c4b67afffcdbe02642c9f
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445505B2

Reaction notes

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