Sodium Bicarbonate → HCID 44243434, compound

HRID 631380Notes

Reaction equation

HRID 631380 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-7469cf8187674625852659c7f6665a70
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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