2,6-Difluoroaniline → HCID 59452831, compound

HRID 419312Notes

Reaction equation

HRID 419312 reaction equation
[CH3:1][N:2]([CH3:40])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([NH:12][C:13]2[N:18]=[C:17]([C:19]3[N:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]4=[N:21][C:20]=3[C:28]3[CH:29]=[CH:30][C:31]([O:38][CH3:39])=[C:32]([CH:37]=3)[C:33](OC)=[O:34])[CH:16]=[CH:15][N:14]=2)[CH:9]=[CH:10][CH:11]=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+].C([O-])(O)=O.[Na+]>C1COCC1>[F:41][C:42]1[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[C:43]=1[NH:44][C:33](=[O:34])[C:32]1[CH:37]=[C:28]([C:20]2[N:21]=[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]3[C:19]=2[C:17]2[CH:16]=[CH:15][N:14]=[C:13]([NH:12][C:8]3[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:40])[CH3:1])[CH:7]=3)[N:18]=2)[CH:29]=[CH:30][C:31]=1[O:38][CH3:39]

Participants

6

Reactant 4

HCID 796472,6-DifluoroanilineHCID 516892Sodium BicarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59452899HCID 59452899, compound

Product 1

HCID 59452831HCID 59452831, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To methyl 5-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzoate (2.35 g, 4.36 mmol) and 2,6-difluoroaniline (2.35 mL, 21.8 mmol) in THF (30 mL) was added sodium bis(trimethylsilyl)amide (26.0 mL, 1M in THF, 26.0 mmol) in one portion. Upon completion by MS, the reaction was poured into half saturated NaHCO3, extracted with DCM and EtOAc, dried (MgSO4) and concentrated. Purification by flash chromatography and trituration with diethyl ether provided the title compound (2.05 g, 3.23 mmol, 74%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.16 (s, 6H), 2.56 (br. s., 2H), 3.98 (br. s., 5H), 6.55 (d, J=7.7 Hz, 1H), 6.69 (d, J=4.4 Hz, 1H), 7.01-7.11 (m, 1H), 7.17 (d, J=7.3 Hz, 3H), 7.27 (s, 2H), 7.32-7.42 (m, 1H), 7.42-7.54 (m, 2H), 7.74 (d, J=8.8 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 8.15 (s, 1H), 8.37 (d, J=4.4 Hz, 1H), 9.49 (br. s., 1H), 9.78 (d, J=12.5 Hz, 2H). MS (M+H, ES+) 636.

Workup

  1. extractionextracted with DCM and EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by flash chromatography and trituration with diethyl ether

Sources & evidence

ORD record
ord-6a65d88b0f184943b1ff3427c452d388
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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