2,6-Difluoroaniline → HCID 59453010, compound

HRID 419374Notes

Reaction equation

HRID 419374 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:15][C:16]1[N:21]=[C:20]([C:22]2[N:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]3=[N:24][C:23]=2[C:31]2[CH:32]=[C:33]([CH:38]=[CH:39][CH:40]=2)[C:34]([O:36]C)=O)[CH:19]=[CH:18][N:17]=1.[F:41][C:42]1[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[C:43]=1[NH2:44].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[F:41][C:42]1[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[C:43]=1[NH:44][C:34](=[O:36])[C:33]1[CH:38]=[CH:39][CH:40]=[C:31]([C:23]2[N:24]=[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]3[C:22]=2[C:20]2[CH:19]=[CH:18][N:17]=[C:16]([NH:15][C:4]3[CH:5]=[CH:6][C:7]([N:9]4[CH2:14][CH2:13][O:12][CH2:11][CH2:10]4)=[CH:8][C:3]=3[O:2][CH3:1])[N:21]=2)[CH:32]=1

Participants

5

Reactant 3

HCID 796472,6-DifluoroanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59452700HCID 59452700, compound

Product 1

HCID 59453010HCID 59453010, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl 3-[3-(2-{[2-(methyloxy)-4-(4-morpholinyl)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzoate (65 mg, 0.12 mmol) in 2 mL THF was added 2,6-difluoroaniline (0.065 mL, 0.60 mmol) and a 1M solution of NaHMDS in THF (0.72 mL, 0.72 mmol). When LC/MS showed the reaction to be complete it was concentrated onto silica gel and purified by flash column chromatography to give 57 mg (75%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 9.38 (s, 1H), 8.45 (s, 1H), 8.27 (s, 1H), 8.18 (d, J=5.2 Hz, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.78 (d, J=7.2 Hz, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.60-7.52 (m, 2H), 7.47-7.40 (m, 2H), 7.35-7.30 (m, 1H), 7.11-7.07 (m, 1H), 6.98-6.94 (m, 1H), 6.67 (s, 1H), 6.48-6.43 (m, 2H), 3.78 (s, 3H), 3.73-3.72 (m, 4H), 3.10-3.09 (m, 4H). MS (ESI) m/z=634 [M+H]+.

Workup

  1. customthe reaction
  2. concentrationwas concentrated onto silica gel
  3. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-5536d3adc7394e4181133ec16dc54a0a
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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