Dimethylamine → 3-(2-Bromo-phenyl)-7-(2-dimethylaminomethyl-2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-1-methyl-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one

HRID 9729Notes

Reaction equation

HRID 9729 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13]([NH:18][C:19]3[CH:40]=[CH:39][C:22]4[O:23][CH:24]([CH2:27]OS(C5C=CC(C)=CC=5)(=O)=O)[CH2:25][O:26][C:21]=4[CH:20]=3)=[N:14][CH:15]=2)[N:10]([CH3:41])[C:9]1=[O:42].[CH3:43][NH:44][CH3:45]>CN1C(=O)CCC1.C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13]([NH:18][C:19]3[CH:40]=[CH:39][C:22]4[O:23][CH:24]([CH2:27][N:44]([CH3:45])[CH3:43])[CH2:25][O:26][C:21]=4[CH:20]=3)=[N:14][CH:15]=2)[N:10]([CH3:41])[C:9]1=[O:42]

Participants

5

Reactant 2

HCID 674DimethylamineHCID 865921593-(2-bromo-phenyl)-3,4-dihydro-7-[2-(p-toluenesulfonyl)oxymethyl-benzodioxane-6 yl]amino-1-methyl-pyrimido[4,5-d]pyrimidin-2 (1H)-one

Product 1

HCID 104819533-(2-Bromo-phenyl)-7-(2-dimethylaminomethyl-2,3-dihydro-benzo[1,4]dioxin-6-ylamino)-1-methyl-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

90 mg of the tosylate from example 4 in 8 ml NMP were treated with 0.62 ml 2 M dimethylamine in THF and stirred at room temperature for 3 d. The mixture was heated to 50° C. for 4 hrs, then to 65° C. for another 2 hrs. Stirring was continued at 45° C. over night. Separation by HPLC-MS yielded crude product contaminated by NMP, which was further purified by dissolving in CHCl3 and washing with water.

Workup

  1. temperatureThe mixture was heated to 50° C. for 4 hrs
  2. waitto 65° C. for another 2 hrs
  3. stirringStirring
  4. waitwas continued at 45° C. over night
  5. customSeparation by HPLC-MS
  6. customyielded crude product
  7. customwas further purified
  8. dissolutionby dissolving in CHCl3
  9. washwashing with water

Sources & evidence

ORD record
ord-a19fcdf6ed754c9987d55b1d13e1762c
Source dataset
uspto-grants-2006_08
Patent number
US07091345B2

Reaction notes

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