Methyl iodide → HCID 178483066, compound

HRID 1984886Notes

Reaction equation

HRID 1984886 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH2:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([CH2:19][NH:20][C:21]3[N:30]=[C:29]([N:31]([CH3:33])[CH3:32])[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)[CH2:15][CH2:14]2)(=[O:10])=[O:9])=[C:4]([O:34][C:35]([F:38])([F:37])[F:36])[CH:3]=1.[H-].[Na+].I[CH3:42]>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([CH2:19][NH:20][C:21]3[N:30]=[C:29]([N:31]([CH3:33])[CH3:32])[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)[CH2:15][CH2:14]2)[CH3:42])(=[O:10])=[O:9])=[C:4]([O:34][C:35]([F:36])([F:37])[F:38])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178483067HCID 178483067, compound

Product 1

HCID 178483066HCID 178483066, compoundYield 69.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of trans-4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-2-trifluoromethoxy-benzenesulfonamide obtained in step H of example 1 (380 mg, 0.61 mmol) in DMF (2 mL) was added 60% sodium hydride in oil (24.6 mg, 0.61 mmol). The reaction mixture was stirred at ambient temperature for 80 min. The reaction mixture was cooled at 0° C. and iodomethane (38.3 μL, 0.61 mmol) was added and stirred at ambient temperature for 3 hr. The reaction was quenched with saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, 25% EtOAc in hexane, and silica gel, 5% MeOH in CHCl3) to give trans-4-bromo-N-{4-[(4-dimethylamino-quinazolin-2-ylamino)-methyl]-cyclohexylmethyl}-N-methyl-2-trifluoromethoxy-benzenesulfonamide (268 mg, 69%) as a pale yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled at 0° C.
  2. stirringstirred at ambient temperature for 3 hr
  3. customThe reaction was quenched with saturated aqueous NaHCO3
  4. extractionThe aqueous layer was extracted with EtOAc (three times)
  5. dry with materialThe combined organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by flash chromatography (NH-silica gel, 25% EtOAc in hexane, and silica gel, 5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-c8c7dd8698f2406194f93980ac71d6f1
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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