1,2-Difluoro-4-(methylsulfonyl)benzene → 3,4-difluoro-2-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile
Reaction equation
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[CH:22]=[CH:21][NH:20][C:19](=[O:23])[CH:18]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].C(C1[CH:27]=[N:28]C(N2CCC(OC3C=CNC(=O)C=3)CC2)=NC=1)C.[F:46][C:47]1[CH:52]=[CH:51][C:50](S(C)(=O)=O)=[CH:49][C:48]=1[F:57]>>[F:57][C:48]1[C:49]([N:20]2[CH:21]=[CH:22][C:17]([O:16][CH:13]3[CH2:14][CH2:15][N:10]([C:7]4[N:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][N:6]=4)[CH2:11][CH2:12]3)=[CH:18][C:19]2=[O:23])=[C:50]([CH:51]=[CH:52][C:47]=1[F:46])[C:27]#[N:28]Participants
Reactant 3
Product 1
Procedure
Example 252 was prepared according to procedures described in Example 248 substituting 4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one (prepared according to procedures described in Example 173 Step C) for 4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one and substituting 2,3,4-trifluorobenzonitrile (Oakwood) for 1,2-difluoro-4-(methylsulfonyl)benzene. 1H NMR (400 MHz, CDCl3) δ ppm 8.10 (s, 2H), 7.43-7.60 (m, 1H), 7.27-7.43 (m, 1H), 7.02 (d, J=7.78 Hz, 1 H), 6.05 (dd, J=7.65, 2.64 Hz, 1 H), 5.96 (d, J=2.51 Hz, 1H), 4.43-4.60 (m, 1 H), 4.08-4.24 (m, 2 H), 3.49-3.66 (m, 2H), 2.34 (t, J=7.53 Hz, 2 H), 1.99-2.08 (m, 2 H), 1.71-1.88 (m, 2 H), 1.43-1.59 (m, 2 H), 0.87 (t, J=7.28 Hz, 3 H). MS (ESI) 452 (M+H).
Workup
- customExample 252 was prepared
Sources & evidence
- ORD record
- ord-c2a60e21f8504962a384dd2608a4692f
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08232404B2
Reaction notes
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