Water → HCID 46909061, compound

HRID 1183204Notes

Reaction equation

HRID 1183204 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[N:13]([CH3:14])[CH:12]=[N:11][C:10]=2[C:15]2[CH:20]=[CH:19][C:18]([C@H:21]3[CH2:23][C@@H:22]3[C:24]([NH:26][CH2:27][CH2:28][F:29])=[O:25])=[CH:17][CH:16]=2)=[N:6][CH:7]=1.[H-].[Na+].I[CH3:33].O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:9]2[N:13]([CH3:14])[CH:12]=[N:11][C:10]=2[C:15]2[CH:20]=[CH:19][C:18]([C@H:21]3[CH2:23][C@@H:22]3[C:24]([N:26]([CH2:27][CH2:28][F:29])[CH3:33])=[O:25])=[CH:17][CH:16]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 46909060HCID 46909060, compound

Product 1

HCID 46909061HCID 46909061, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 10 (10 mg, 0.023 mmol) in DMF (1 Ml) was added sodium hydride (60% in mineral oil), (6 mg, 0.139 mmol) and iodomethane (0.009 Ml, 0.139 mmol). The reaction mixture was stirred at rt for 30 min Water was added and the mixture was extracted with ethyl acetate. The organics were dried (MgSO4), concentrated, and purified on 4 g of silica gel eluting a gradient of 0-5% triethylamine in ethyl acetate to give rise to the title compound. 1H NMR (500 MHz), [CD3OD]: 8.34 (s, 1H), 8.04 (s, 1H), 7.73 (m, 2H), 7.63 (d, 1H), 7.14 (m, 2H), 6.92 (d, 1H), 4.58 (m, 1H), 4.48 (m, 1H), 3.66 (s, 3H), 3.19 (s, 3H), 3.00 (br, 2H), 2.37 (m, 1H), 2.18 (m, 1H), 1.53 (m, 1H), 1.31 (m, 1H). LCMS: [M+1]+=445. Human FAAH lysate assay: IC50=3.0 nM.

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe organics were dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified on 4 g of silica gel eluting a gradient of 0-5% triethylamine in ethyl acetate

Sources & evidence

ORD record
ord-a1a4d04288b2480f8e26cf0232a8e102
Source dataset
uspto-grants-2014_03
Patent number
US08664253B2

Reaction notes

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