1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-{3-(Cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide

HRID 1049141Notes

Reaction equation

[CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[C:15]([CH:17]=[C:18]1[CH2:21][N:20]([C:22]2[C:36]([F:37])=[CH:35][C:25]([C:26]([NH:28][C@@H:29]([CH3:34])[C:30]([F:33])([F:32])[F:31])=[O:27])=[C:24]([F:38])[CH:23]=2)[CH2:19]1)#[N:16].N12CCCN=C1CCCCC2>C(#N)C>[C:15]([CH2:17][C:18]1([N:12]2[CH:13]=[C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]3)[CH:10]=[N:11]2)[CH2:21][N:20]([C:22]2[C:36]([F:37])=[CH:35][C:25]([C:26]([NH:28][C@@H:29]([CH3:34])[C:30]([F:33])([F:31])[F:32])=[O:27])=[C:24]([F:38])[CH:23]=2)[CH2:19]1)#[N:16]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.00 g, 5.15 mmol), 4-[3-(cyanomethylene)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide (1.78 g, 5.15 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.31 mL, 2.1 mmol) in acetonitrile (20.2 mL) was heated at 50° C. overnight. After cooling, the solvent was removed under reduced pressure. The residue was used in the next step without further purification. LCMS cacld. for C24H28BF5N5O3 (M+1)+: m/z=540.2. Found: 540.1.

Workup

temperatureAfter cooling
customthe solvent was removed under reduced pressure
customThe residue was used in the next step without further purification

Sources & evidence

ORD record: ord-2495739a463d4a2dac43787830234dbc
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382231B2

Reaction notes

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