Water → HCID 89884776, compound

HRID 572139Notes

Reaction equation

HRID 572139 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:8]([C@@H:18]([NH:23][C:24]1[C:25]3[N:33]=[CH:32][CH:31]=[CH:30][C:26]=3[N:27]=[CH:28][N:29]=1)[C:19]([F:22])([F:21])[F:20])=[CH:7]2.[H-].[Na+].[CH3:36]I.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:8]([C@@H:18]([N:23]([C:24]1[C:25]3[N:33]=[CH:32][CH:31]=[CH:30][C:26]=3[N:27]=[CH:28][N:29]=1)[CH3:36])[C:19]([F:22])([F:21])[F:20])=[CH:7]2

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 56929568HCID 56929568, compound

Product 1

HCID 89884776HCID 89884776, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of Example 1 (92 mg, 0.197 mmol) in DMF (10 mL) was cooled to 0° C. NaH (60%; 9 mg, 0.217 mmol) was added and the mixture was stirred at 0° C. for 5 minutes. Methyl iodide (30 mg, 0.207 mmol) was added and the mixture was stirred at r.t. for 16 h. Water (0.5 mL) was added and the mixture was evaporated in vacuo. The residue was partitioned between DCM and water. The aqueous phase was extracted with further DCM, the combined organic fractions were washed with brine and dried Na2SO4), then the solvent was evaporated in vacuo. The residue was purified twice by column chromatography (SiO2, 0-35% MeOH in EtOAc) to give the title compound (16 mg, 17%) as an off-white solid. δH (DMSO-d6) 9.00 (d, J 1.7 Hz, 1H), 8.77 (dd, J 4.8, 1.6 Hz, 1H), 8.73-8.70 (m, 2H), 8.27 (dt, J 7.8, 1.8 Hz, 1H), 8.11 (dd, J 8.3, 1.2 Hz, 1H), 8.01 (s, 1H), 7.98 (dd, J 7.5, 1.2 Hz, 1H), 7.85 (dd, J 8.5, 1.2 Hz, 1H), 7.71 (dd, J 8.5, 4.4 Hz, 1H), 7.66-7.56 (m, 2H), 5.93 (q, J 7.7 Hz, 1H), 3.53 (s, 3H). LCMS (ES+) 481 (M+H)+, RT 2.31 minutes.

Workup

  1. stirringthe mixture was stirred at r.t. for 16 h
  2. customthe mixture was evaporated in vacuo
  3. customThe residue was partitioned between DCM and water
  4. extractionThe aqueous phase was extracted with further DCM
  5. washthe combined organic fractions were washed with brine and dried Na2SO4), then the solvent
  6. customwas evaporated in vacuo
  7. customThe residue was purified twice by column chromatography (SiO2, 0-35% MeOH in EtOAc)

Sources & evidence

ORD record
ord-7dec48ddb82d49fa929f1b437f09e63e
Source dataset
uspto-grants-2015_05
Patent number
US09029392B2

Reaction notes

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