Sodium Bicarbonate → HCID 44243434, compound

HRID 871425Notes

Reaction equation

HRID 871425 reaction equation
C([O-])(O)=O.[Na+].FC(F)(F)S(O[CH2:12][CH:13]([F:15])[F:14])(=O)=O.Cl.Cl.[C:20]([C:24]1[O:28][N:27]=[C:26]([NH:29][C:30]([NH:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([O:39][C:40]3[C:49]4[C:44](=[CH:45][C:46]([O:56][CH3:57])=[C:47]([O:50][C@H:51]5[CH2:55][CH2:54][NH:53][CH2:52]5)[CH:48]=4)[N:43]=[CH:42][N:41]=3)[CH:34]=2)=[O:31])[CH:25]=1)([CH3:23])([CH3:22])[CH3:21]>C(OCC)(=O)C>[C:20]([C:24]1[O:28][N:27]=[C:26]([NH:29][C:30]([NH:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([O:39][C:40]3[C:49]4[C:44](=[CH:45][C:46]([O:56][CH3:57])=[C:47]([O:50][C@H:51]5[CH2:55][CH2:54][N:53]([CH2:12][CH:13]([F:15])[F:14])[CH2:52]5)[CH:48]=4)[N:43]=[CH:42][N:41]=3)[CH:34]=2)=[O:31])[CH:25]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 66877193HCID 66877193, compound

Product 1

HCID 44243434HCID 44243434, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

To a mixture of a solution of NaHCO3 (47 mg in 1.5 mL, 0.561 mmol) and ethyl acetate (3 mL), 2,2-difluoroethyl trifluoromethanesulfonate (48 μL, 0.22 mmol) was added. After heating at 40 C, (S)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(pyrrolidin-3-yloxy)quinazolin-4-yloxy)phenyl)urea dihydrochloride (110 mg, 0.187 mmol) was added. The reaction mixture was stirred at 40° C. for 1 h. The mixture was diluted with ethyl acetate and organic layer was washed with brine. After drying over MgSO4, the solvent was evaporated and the crude product purified on silica gel, using dichloromethane/methanol as mobile phase. Yield: 40 mg (37%). 1HNMR (dmso-d6): δ 9.58 (1H, s), 9.00 (1H, s), 8.56 (1H, s), 7.59 (1H, s), 7.47 (1H, s), 7.40 (2H, m), 7.25 (1H, d), 6.97 (1H, d), 6.48 (1H, s), 5.15 (1H, m), 5.15 (1H, m), 3.99 (3H, s), 2.91 (6H, m), 2.40 (1H, m), 1.90 (1H, m), 1.27 (9H, s). LC-MS (ESI) m/z 583 (M+H)+.

Workup

  1. additionwas added
  2. additionwas added
  3. washwas washed with brine
  4. dry with materialAfter drying over MgSO4
  5. customthe solvent was evaporated
  6. customthe crude product purified on silica gel

Sources & evidence

ORD record
ord-98d7ed3eb40148c3b9c23eb935652d9b
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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