p-(Trifluoromethoxy)benzaldehyde → HCID 44629182, compound
Reaction equation
C(N(C(C)C)CC)(C)C.Cl.[CH:11]1([NH:14][C:15](=[O:28])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[CH2:23][CH2:24][NH:25][CH2:26][CH:27]=3)[N:17]=2)[CH2:13][CH2:12]1.[F:29][C:30]([F:41])([F:40])[O:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=1.[BH3-]C#N.[Na+]>>[CH:11]1([NH:14][C:15]([C:16]2[N:17]=[C:18]([C:22]3[CH2:23][CH2:24][N:25]([CH2:36][C:35]4[CH:38]=[CH:39][C:32]([O:31][C:30]([F:29])([F:40])[F:41])=[CH:33][CH:34]=4)[CH2:26][CH:27]=3)[CH:19]=[CH:20][CH:21]=2)=[O:28])[CH2:13][CH2:12]1Participants
Procedure
1′-(4-Trifluoromethoxybenzyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide (9) was prepared by adding diisopropyl ethyl amine to a suspension of compound 5 (72 mg, 0.25 mmol), 4-trifluoromethoxybenzaldehyde (8) (Aldrich) and 3 Å molecular sieves (200 mg, Aldrich). The mixture was stirred for 12 hours and NaCNBH3 was added. The crude product was filtered and then purified on Prep TLC (10% MeOH in dichloromethane with 1% NH4OH) to provide the title compound 9 (25 mg, yield 23%): 1H NMR (400 MHz, CD3OD, HCl-salt): δ 8.48 (bd, 1 h, NH), 7.88 (d, 1H, J=7.6 Hz), 7.83 (t, 1H, J=7.6 Hz), 7.65 (d, 1H, J=7.6 Hz), 7.57 (m, 2H), 7.32 (d, 2H, J=8.8 Hz), 6.68 (m, 1H), 4.39 (m, 2H), 3.85 (m, 2H), 3.68 (m, 1H), 3.26 (m, 1H), 3.12 (m, 1H), 2.82 (m, 1H), 2.71 (m, 1H), 0.72 m, 2H), 0.54 (m, 2H); MS: 418.
Workup
- custom1′-(4-Trifluoromethoxybenzyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide (9) was prepared
- filtrationThe crude product was filtered
- custompurified on Prep TLC (10% MeOH in dichloromethane with 1% NH4OH)
Sources & evidence
- ORD record
- ord-b204720c8f164689893e82694c951f4b
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08324249B2
Reaction notes
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