Hydrochloric Acid → N2-((4-chloro-1H-benzo[d]imidazol-5-yl)methyl)-N4-(5-(difluoromethyl)-1H-pyrazol-3-yl)-N2-methylpyrimidine-2,4-diamine

HRID 475311Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]([F:16])[F:15])[NH:11][N:10]=2)[CH:5]=[CH:4][N:3]=1.Cl.[Cl:18][C:19]1[C:27]2[N:26]=[CH:25][N:24](C3CCCCO3)[C:23]=2[CH:22]=[CH:21][C:20]=1[CH2:34][NH:35][CH3:36].CCN(C(C)C)C(C)C.Cl.O1CCOCC1>CCCCO>[Cl:18][C:19]1[C:27]2[N:26]=[CH:25][NH:24][C:23]=2[CH:22]=[CH:21][C:20]=1[CH2:34][N:35]([CH3:36])[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]([F:16])[F:15])[NH:11][N:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A vial was charged with 2-chloro-N-(5-(difluoromethyl)-1H-pyrazol-3-yl)pyrimidin-4-amine (80 mg, 0.33 mmol), the bis HCl salt of 1-(4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)-N-methylmethanamine (138 mg, 0.39 mmol), DIPEA (0.29 mL, 1.63 mmol) and n-BuOH (1.5 mL), sealed and heated at 90° C. for 8 h. The reaction mixture was then cooled to RT, and 4N HCl/dioxane (0.81 mL, 3.26 mmol) was added. The mixture was stirred at 40° C. for 3 h and then concentrated in vacuo. The crude mixture was purified by preparative HPLC to afford 15.1 Mg9 12%) of N2-((4-chloro-1H-benzo[d]imidazol-5-yl)methyl)-N4-(5-(difluoromethyl)-1H-pyrazol-3-yl)-N2-methylpyrimidine-2,4-diamine (II-81).

Workup

temperatureThe reaction mixture was then cooled to RT
concentrationconcentrated in vacuo
customThe crude mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-4ad634344f1c4f0ca17934bdbb5e551c
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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