Methyl iodide → N-[4-Methyl-3-(1-methyl-7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 2222253Notes

Reaction equation

HRID 2222253 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:22])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[CH:6][C:5]=1[N:23]1[C:32](=[O:33])[C:31]2[C:26](=[N:27][C:28]([S:34][CH3:35])=[N:29][CH:30]=2)[NH:25][C:24]1=[O:36].I[CH3:38]>CN(C=O)C.C(OCC)(=O)C>[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:22])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:19])([F:20])[F:21])[CH:13]=2)=[CH:6][C:5]=1[N:23]1[C:32](=[O:33])[C:31]2[C:26](=[N:27][C:28]([S:34][CH3:35])=[N:29][CH:30]=2)[N:25]([CH3:38])[C:24]1=[O:36]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68522440N-[4-Methyl-3-(7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamide

Product 1

HCID 68527350N-[4-Methyl-3-(1-methyl-7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamideYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the suspension of NaH (60% dispersion in mineral oil, 19.7 mg, 0.49 mmol) in DMF is added N-[4-Methyl-3-(7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamide (218 mg, 0.45 mmol) at 0° C. When H2 evolution has ceased, iodomethane (84 μl, 1.35 mmol) is added and the reaction mixture is stirred for 3 hours at room temperature. The mixture is diluted with ethyl acetate, and washed with 5% aqueous Na2S2O3 solution to remove DMF. The organic layer is dried over MgSO4 and concentrated under reduced pressure. The crude product is crystallized from MeOH to give N-[4-Methyl-3-(1-methyl-7-methylsulfanyl-2,4-dioxo-1,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-3-yl)-phenyl]-3-trifluoromethyl-benzamide (184 mg, 82%) as a white solid.

Workup

  1. washwashed with 5% aqueous Na2S2O3 solution
  2. customto remove DMF
  3. dry with materialThe organic layer is dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product is crystallized from MeOH

Sources & evidence

ORD record
ord-e1216cf3cb4c4d9e91ef5c5ccc07fc40
Source dataset
uspto-grants-2008_05
Patent number
US07371750B2

Reaction notes

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