Pyrazole → HCID 49869216, compound

HRID 450199Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=3[N:16]=[C:15]2[CH:25]([F:27])[F:26])[N:3]=1.[NH:28]1[CH:32]=[CH:31][CH:30]=[N:29]1.CCN(C(C)C)C(C)C>O>[F:26][CH:25]([F:27])[C:15]1[N:14]([C:4]2[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=[C:2]([N:28]3[CH:32]=[CH:31][CH:30]=[N:29]3)[N:3]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[N:16]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) (0.49 mg, 1.22 mmol), 1H-pyrazole (1.0 g, 14.7 mmol), and DIPEA (3 mL) was heated to 120° C. for 40 min, cooled to 20° C., and diluted with water (50 mL). The resulting precipitate was collected by filtration, washed with water, and dried. Chromatography on silica, eluting with CH2Cl2/EtOAc (4:1), gave 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1H-pyrazol-1-yl)-1,3,5-triazin-2-yl]-1H-benzimidazole (428 mg, 82%): mp (CH2Cl2/hexanes) 274-277° C.; 1H NMR (DMSO-d6) δ 8.79 (dd, J=2.8, 0.5 Hz, 1H), 8.14 (dd, J=8.3, 0.5 Hz, 1H), 8.01 (d, J=0.8 Hz, 1H), 7.88 (t, J=52.8 Hz, 1H), 7.49 (t, J=8.2 Hz, 1H), 7.02 (d, J=7.8 Hz, 1H), 6.70 (dd, J=2.8, 1.5 Hz, 1H), 4.01 (m, 2H), 4.00 (s, 3H), 3.93 (m, 2H), 3.80-3.75 (m, 4H); Anal. Calcd. for C19H18F2N8O2: C, 53.3; H, 4.2; N, 26.2. Found: C, 53.1; H, 4.1; N, 25.9%.

Workup

temperaturecooled to 20° C.
filtrationThe resulting precipitate was collected by filtration
washwashed with water
customdried
washChromatography on silica, eluting with CH2Cl2/EtOAc (4:1)

Sources & evidence

ORD record: ord-f9ccfa3766914c2fa4166632228e6d04
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486939B2

Reaction notes

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