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

HRID 488416Notes

Reaction equation

HRID 488416 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]([OH:12])=O)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][C:45]=1[O:46][CH2:47][CH:48]1[CH2:50][CH2:49]1)[N:42]=[CH:41][N:40]=[C:39]2[NH:51][C:52]1[CH:57]=[CH:56][C:55]([F:58])=[C:54]([Cl:59])[CH:53]=1.C(N(CC)CC)C>CN(C)C=O>[Cl:59][C:54]1[CH:53]=[C:52]([NH:51][C:39]2[C:38]3[C:43](=[CH:44][C:45]([O:46][CH2:47][CH:48]4[CH2:49][CH2:50]4)=[C:36]([NH:35][C:10](=[O:12])[CH2:9][P:4]([O:3][CH2:1][CH3:2])([O:6][CH2:7][CH3:8])=[O:5])[CH:37]=3)[N:42]=[CH:41][N:40]=2)[CH:57]=[CH:56][C:55]=1[F:58]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 36704(Diethoxyphosphinyl)acetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 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

137 mg (diethoxyphosphoryl)-acetic acid and 225 mg benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate are added subsequently to a solution of 200 mg 6-amino-4-[(3-chloro-4-fluoro-phenyl)amino]-7-cyclopropylmethoxy-quinazoline and 0.11 ml triethylamine in 1 ml of anhydrous N,N-dimethyl-formamide. The reaction mixture is stirred for one hour at room temperature, quenched with 10 ml of water, and extracted with ethyl acetate/methanol (10:1). The combined extracts are washed with water and brine, dried over magnesium sulfate, and concentrated in vacuo. The crude product is recrystallized from diethyl ether. Yield: 190 mg (64% of theory), Melting point: 185-187° C. Mass spectrum (ESI*): m/z=537, 539 [M+H]*

Workup

  1. customquenched with 10 ml of water
  2. extractionextracted with ethyl acetate/methanol (10:1)
  3. washThe combined extracts are washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product is recrystallized from diethyl ether

Sources & evidence

ORD record
ord-f788b6bd259445bcb0e692efdd7bc1fa
Source dataset
uspto-grants-2005_12
Patent number
US06972288B1

Reaction notes

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