Water → 4-[(3-Chloro-4-fluorophenyl)amino]-6-({[(diethoxyphosphoryl)methyl]carbonyl}amino)-7-cyclopropylmethoxyquinazoline

HRID 1168691Notes

Reaction equation

HRID 1168691 reaction equation
C(N(CC)CC)C.[CH2:8]([O:10][P:11]([CH2:16][C:17]([OH:19])=O)([O:13][CH2:14][CH3:15])=[O:12])[CH3:9].[NH2:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][C:30]=1[O:31][CH2:32][CH:33]1[CH2:35][CH2:34]1)[N:27]=[CH:26][N:25]=[C:24]2[NH:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([Cl:44])[CH:38]=1.O>CN(C)C=O>[Cl:44][C:39]1[CH:38]=[C:37]([NH:36][C:24]2[C:23]3[C:28](=[CH:29][C:30]([O:31][CH2:32][CH:33]4[CH2:34][CH2:35]4)=[C:21]([NH:20][C:17]([CH2:16][P:11]([O:10][CH2:8][CH3:9])([O:13][CH2:14][CH3:15])=[O:12])=[O:19])[CH:22]=3)[N:27]=[CH:26][N:25]=2)[CH:42]=[CH:41][C:40]=1[F:43]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 36704(Diethoxyphosphinyl)acetic acidHCID 155418526-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxyquinazoline

Product 1

HCID 222700574-[(3-Chloro-4-fluorophenyl)amino]-6-({[(diethoxyphosphoryl)methyl]carbonyl}amino)-7-cyclopropylmethoxyquinazoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.77 ml of triethylamine, 3.43 g of diethoxyphosphorylacetic acid, and 5.62 g of benzotriazol-1-yl-N-tetramethyluronium tetrafluoroborate are added successively to 5.00 g of 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxyquinazoline in 25 ml of N,N-dimethylformamide. The reaction mixture is stirred for one hour at ambient temperature; 250 ml of water is then added and the mixture is extracted with 250 ml of ethyl acetate/methanol (10:1). The organic phase is washed with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated by evaporation. The residue in the flask is crystallized by stirring with diethylether.

Workup

  1. extractionthe mixture is extracted with 250 ml of ethyl acetate/methanol (10:1)
  2. washThe organic phase is washed with water and saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated by evaporation
  5. customThe residue in the flask is crystallized
  6. stirringby stirring with diethylether

Sources & evidence

ORD record
ord-da96f69141ab4323bc24d9db2370aa03
Source dataset
uspto-grants-2003_09
Patent number
US06627634B2

Reaction notes

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