1,8-Diazabicyclo(5.4.0)undec-7-ene → N-[3-(5-{1-[1-(cyanomethyl)-2,2,2-trifluoroethyl]-1H-pyrazol-4-yl}-1H-benzimidazol-1-yl)phenyl]-N'-(2,2,2-trifluoroethyl)urea

HRID 406993Notes

Reaction equation

Cl.[NH:2]1[CH:6]=[C:5]([C:7]2[CH:30]=[CH:29][C:10]3[N:11]([C:14]4[CH:15]=[C:16]([NH:20][C:21]([NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[O:22])[CH:17]=[CH:18][CH:19]=4)[CH:12]=[N:13][C:9]=3[CH:8]=2)[CH:4]=[N:3]1.[F:31][C:32]([F:38])([F:37])/[CH:33]=[CH:34]/[C:35]#[N:36].N12CCCN=C1CCCCC2>C(#N)C>[C:35]([CH2:34][CH:33]([N:2]1[CH:6]=[C:5]([C:7]2[CH:30]=[CH:29][C:10]3[N:11]([C:14]4[CH:15]=[C:16]([NH:20][C:21]([NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[O:22])[CH:17]=[CH:18][CH:19]=4)[CH:12]=[N:13][C:9]=3[CH:8]=2)[CH:4]=[N:3]1)[C:32]([F:38])([F:37])[F:31])#[N:36]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of N-{3-[5-(1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea HCl salt (20.0 mg, 0.0458 mmol) in acetonitrile (1 mL) was added (2E)-4,4,4-trifluorobut-2-enenitrile (8.3 mg, 0.069 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (14 μL, 0.092 mmol). The solution was stirred and heated at 80° C. for several hours. The reaction solution was concentrated under reduced pressure to dryness. The residue was dissolved in MeOH, and purified by RP-HPLC (pH=10) to afford the desired compound. LCMS (M+H)+: m/z=522.1.

Workup

concentrationThe reaction solution was concentrated under reduced pressure to dryness
dissolutionThe residue was dissolved in MeOH
custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record: ord-4990299534f64d9eaf5046fe30e475f9
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754114B2

Reaction notes

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