p-Toluenesulfonic acid → HCID 68912489, compound

HRID 1517421Notes

Reaction equation

HRID 1517421 reaction equation
C([NH:4][C:5]1[NH:6][C:7](=O)[C:8]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([CH3:22])[CH:16]=3)[CH:12]=[CH:11][C:9]=2[N:10]=1)(=O)C.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.S([O-])([O-])(=O)=O.[NH4+].[NH4+].C[Si](C)(C)N[Si](C)(C)C.[O-]CC.[Na+]>C1(C)C=CC=CC=1.ClCCl.C(O)C>[NH2:4][C:5]1[N:6]=[C:7]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:8]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([CH3:22])[CH:16]=3)[CH:12]=[CH:11][C:9]=2[N:10]=1

Participants

10

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 8083MorpholineHCID 13838HexamethyldisilazaneHCID 2723922Sodium ethoxideHCID 6097028Ammonium SulfateHCID 136397030HCID 136397030, compound

Product 1

HCID 68912489HCID 68912489, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

to a suspension of 2-acetamido-6-(3-methyl-4-fluorophenyl)-pyrido[3,2-d]pyrimidin-4(3H)-one (312 mg, 1 mmol) in toluene (10 ml) was added morpholine (4 mmol, 0.23 ml), p-toluene sulfonic acid (0.1 mmol, 19 mg), ammonium sulfate (13 mg, 0.1 mmol) and 1,1,1,3,3,3-hexamethyldisilazane (2 ml, 8 mmol). The reaction mixture was refluxed for 48 hours till a brown solution was formed. The solvents were evaporated in vacuo, yielding crude 2-acetamido-4-(morpholino)-6-(4-methyl-3-fluoro-phenyl)-pyrido[3,2-d]pyrimidine. The residue was redissolved in a mixture of dichloromethane and ethanol (in a ratio of 80/20, 10 ml). A sodium ethoxide solution (0.2 N solution) was added till pH 12 and the resulting mixture was stirred overnight at room temperature. The solvents were evaporated in vacuo. The crude residue was purified by preparative TLC on silica, using a methanol/dichloromethane mixture in a ratio of 10:90 as mobile phase, yielding pure 2-amino-4-(morpholino)-6-(3-methyl-4-fluoro-phenyl)-pyrido[3,2-d]pyrimidine (80 mg, yield: 25%).

Workup

  1. temperatureThe reaction mixture was refluxed for 48 hours till a brown solution
  2. customwas formed
  3. customThe solvents were evaporated in vacuo
  4. customyielding crude 2-acetamido-4-(morpholino)-6-(4-methyl-3-fluoro-phenyl)-pyrido[3,2-d]pyrimidine
  5. customThe solvents were evaporated in vacuo
  6. customThe crude residue was purified by preparative TLC on silica

Sources & evidence

ORD record
ord-f2f1d0f9af26479bacc386805154da6a
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

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