1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 178485738, compound

HRID 1749425Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][C:17]=2[C:18]([F:21])([F:20])[F:19])[N:3]=1.[CH3:22][NH:23][C:24]([CH:26]1[CH2:31][CH2:30][CH:29]([NH2:32])[CH2:28][CH2:27]1)=[O:25].N12CCCN=C1CCCCC2>C1COCC1>[C:8]([C:7]1[C:2]([NH:32][C@@H:29]2[CH2:28][CH2:27][C@H:26]([C:24]([NH:23][CH3:22])=[O:25])[CH2:31][CH2:30]2)=[N:3][C:4]([NH:10][CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][C:17]=2[C:18]([F:21])([F:20])[F:19])=[N:5][CH:6]=1)#[N:9]

Participants

Conditions

Temperature: 60 °C

Procedure

4-Chloro-2-(((4-(trifluoromethyl)pyridin-3-yl)methyl)amino)pyrimidine-5-carbonitrile (1.0 equiv.) was placed in a sealable flask with (1s,4s)-4-amino-N-methylcyclohexanecarboxamide (1.0 equiv.), 1,8-diazabicyclo[5.4.0]undec-7-ene (1.2 equiv.), and THF (0.1 M). The flask was purged with nitrogen and sealed. The reaction mixture was heated to 60° C. for 18 h. Standard work-up afforded cis-4-((5-cyano-2-(((4-(trifluoromethyl)pyridin-3-yl)methyl)amino)pyrimidin-4-yl)amino)-N-methylcyclohexanecarboxamide (48.2% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 8.73 (d, J=5.08 Hz, 1H), 8.64-8.69 (m, 1H), 8.29 (t, J=5.66 Hz, 1H), 8.21 (s, 1H), 7.72 (d, J=5.08 Hz, 1H), 7.53-7.66 (m, 1H), 7.00-7.12 (m, 1H), 4.62-4.73 (m, 2H), 3.69 (br. s., 1H), 2.53-2.61 (m, 3H), 2.15-2.30 (m, 1H), 1.70-1.97 (m, 2H), 1.42-1.62 (m, 3H), 1.15-1.27 (m, 3H). MS (ESI) m/z 434.3 [M+1]+

Workup

customThe flask was purged with nitrogen
customsealed

Sources & evidence

ORD record: ord-8ddd1d4fb2a141d893938b62ea527bf0
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

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