Acetic Acid → N-(2,6-difluorophenyl)-3-{3-[2-({2-methyl-4-[(1-methyl-4-piperidinyl)oxy]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide

HRID 419317Notes

Reaction equation

HRID 419317 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:47])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:18]=[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]3[C:25]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH:40]4[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]4)=[CH:35][C:34]=3[CH3:46])[N:27]=2)[CH:12]=1.[C:48](O)(=O)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:47])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:18]=[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]3[C:25]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH:40]4[CH2:45][CH2:44][N:43]([CH3:48])[CH2:42][CH2:41]4)=[CH:35][C:34]=3[CH3:46])[N:27]=2)[CH:12]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59452825N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-(4-piperidinyloxy)phenyl]-amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

Product 1

HCID 59452904N-(2,6-difluorophenyl)-3-{3-[2-({2-methyl-4-[(1-methyl-4-piperidinyl)oxy]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 43.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-(4-piperidinyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide (Example 6) (0.098 g, 0.16 mmol) in DCM (4 mL) and MeOH (2 mL) was added acetic acid (0.20 mL, 1M in DCM, 0.20 mmol) and formaldehyde (0.024 mL, 37% weight in H2O, 0.32 mmol). Sodium triacetoxyborohydride (0.053 g, 0.25 mmol) in one portion and the reaction was stirred at rt until complete by MS. Purification by flash chromatography, followed by preparative HPLC chromatography (prep-HPLC) provided the title compound (0.044 g, 0.070 mmol, 43%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58-1.67 (m, 2H), 1.88-1.95 (m, 2H), 2.11-2.21 (m, 8H), 2.55-2.65 (m, 2H), 4.33 (s, 1H), 6.45 (d, J=5.1 Hz, 1H), 6.81 (d, J=8.1 Hz, 2H), 6.87 (s, 2H), 7.17-7.26 (m, 3H), 7.36-7.47 (m, 2H), 7.62 (t, J=7.8 Hz, 1H), 7.71 (d, J=9.1 Hz, 1H), 7.77-7.85 (m, 1H), 8.06 (d, J=9.5 Hz, 1H), 8.18 (d, J=5.3 Hz, 1H), 8.31 (s, 1H), 8.89 (s, 1H), 9.32 (br. s., 1H). MS (M+H, ES+) 646.

Workup

  1. customPurification by flash chromatography

Sources & evidence

ORD record
ord-4607b0e2e9694e26884e1b6e01194396
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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