Methyl iodide → HCID 59619713, compound

HRID 445678Notes

Reaction equation

HRID 445678 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[C:22]6[CH:28]=[CH:27][NH:26][C:23]6=[N:24][CH:25]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8]2=[O:30])[C:4]([CH3:31])=[N:3]1.[H-].[Na+].I[CH3:35]>CN(C=O)C.CO>[CH3:1][N:2]1[CH:6]=[C:5]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[C:22]6[CH:28]=[CH:27][N:26]([CH3:35])[C:23]6=[N:24][CH:25]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:29])[C:8]2=[O:30])[C:4]([CH3:31])=[N:3]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 49835422HCID 49835422, compound

Product 1

HCID 59619713HCID 59619713, compound

Reagents, catalysts & solvents 2

HCID 887MethanolCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of a new batch of 1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-8-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 36, 45.4 mg, 0.111 mmol) in 1.5 ml anhydrous DMF was treated with 55% NaH in oil (6.0 mg, 0.138 mmol). The reaction mixture was stirred for 20 min at rt, then was added iodomethane (0.009 ml, 138 mmol). The reaction mixture was stirred for 1.5 h at rt. The RM was diluted with MeOH+3 drops TFA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 60:40). The fractions containing products were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting suspension was filtered and the cake was washed with water, before being dried under high vacuum to give the title compound as a white solid. (HPLC: tR 2.62 min (Method A); M+H=424 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.96 (s, 1H), 8.38-8.36 (m, 1H), 8.18-8.16 (m, 1H), 8.13-8.09 (m, 1H), 8.06-8.04 (m, 1H), 7.99-7.95 (m, 1H), 7.60-7.58 (m, 1H), 7.57-7.55 (m, 1H), 6.54-6.51 (m, 1H), 3.93 (s, 3H), 3.85 (s, 3H), 3.58 (s, 3H), 1.97 (s, 3H))

Workup

  1. stirringThe reaction mixture was stirred for 1.5 h at rt
  2. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 60:40)
  3. additionThe fractions containing products
  4. customwere collected together
  5. concentrationbefore being concentrated
  6. filtrationThe resulting suspension was filtered
  7. washthe cake was washed with water
  8. custombefore being dried under high vacuum

Sources & evidence

ORD record
ord-ab7a1f5009144bcda0d2b82f0993a96a
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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