Methyl 2-methylglycidate → 4-(9-Cyclohexyl-7-fluoro-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide
Reaction equation
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([CH3:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:37]=[CH:36][C:25]([C:26]([NH:28][CH:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)=[O:27])=[CH:24][C:23]=4[O:38][CH3:39])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:40]1(NCC(F)(C)C(OCC)=O)CCCCC1.CC1(C(OC)=O)CO1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([CH3:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:37]=[CH:36][C:25]([C:26]([NH:28][CH:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)=[O:27])=[CH:24][C:23]=4[O:38][CH3:39])=[N:20][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:40][CH2:5]1Participants
4
Reactant 3
Product 1
Procedure
The title compound was synthesized using an analogous procedure to that described in connection with Compound 87 except that ethyl 3-(cyclohexylamino)-2-fluoro-2-methylpropanoate, made from commercially available starting material methyl 2-methyloxirane-2-carboxylate, was used and the final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.36 (m, 2H) 1.28-2.08 (m, 17H) 2.19 (s, 3H) 2.81 (d, J=10.6 Hz, 2H) 3.26 (s, 3H) 3.60-3.85 (m, 3H) 3.95 (s, 3H) 4.45 (m, 1H) 7.47 (d, J=8.3 Hz, 1H) 7.50 (s, 1H) 7.75 (s, 1H) 7.97-8.20 (m, 2H) 8.32 (d, J=8.3 Hz, 1H). [M+H] calc'd for C29H40FN7O3, 554. found 554.
Workup
- customthe final compound was purified by reverse phase HPLC
- customto give the free base
Sources & evidence
- ORD record
- ord-aad1721e3259407bbbddbb44000b3308
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08026234B2
Reaction notes
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