Cyclopropanecarboxaldehyde → N-{(1R,2R)-2-[2-(12-sec-Butyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide
Reaction equation
[CH:1]12[NH:12][CH:9]([CH2:10][CH2:11]1)[CH2:8][C:7]1[CH:6]=[CH:5][C:4]([NH:13][C:14]3[N:19]=[C:18]([NH:20][C@@H:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]4[NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[C:17]([Cl:32])=[CH:16][N:15]=3)=[CH:3][C:2]2=1.[CH:33]1([CH:36]=O)[CH2:35][CH2:34]1>>[CH:33]([N:12]1[CH:9]2[CH2:10][CH2:11][CH:1]1[C:2]1[CH:3]=[C:4]([NH:13][C:14]3[N:19]=[C:18]([NH:20][C@@H:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]4[NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[C:17]([Cl:32])=[CH:16][N:15]=3)[CH:5]=[CH:6][C:7]=1[CH2:8]2)([CH2:34][CH3:35])[CH3:36]Participants
Reactant 2
Product 1
Procedure
Following a procedure analogous to 80a, N-{(1R,2R)-2-[2-(12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide (90 mg, 0.19 mmol) and cyclopropanecarbaldehyde (0.056 mL, 0.75 mmol), were converted to the title compound as an off-white solid (69 mg, 69%): 1:1 mixture of diastereomers. 1HNMR (400 MHz, DMSO-d6) δ 9.1 (s, 1H), 7.9 (s, 1H), 7.6 (s, 0.5H), 7.5 (s, 0.5H), 7.3 (m, 1H), 7.2 (d, 0.5H, J=8.6 Hz), 7.1 (d, 0.5H, J=8.3 Hz), 6.9 (d, 1H, J=8.3 Hz), 6.7 (d, 1H, J=8.3 Hz), 4.0 (m, 1H), 3.9-3.8 (m, 1H), 3.5 (m, 1H), 3.4-3.3 (m, 1H), 3.0-2.9 (m, 4H), 2.5-2.4 (m, 1H), 2.3 (d, 1H, J=16.9 Hz), 2.2-2.0 (m, 5H), 1.9 (m, 3H), 1.6-1.2 (m, 6H), 0.9-0.8 (m, 2H), 0.4 (m, 2H); MS (m/e) 531 (M+1); mp 120-124° C.
Sources & evidence
- ORD record
- ord-0945c2dc6d45417ca4c8121c668614be
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08552186B2
Reaction notes
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