Pyridine → Phenyl 4-(3-ethynylphenylamino)-7-fluoroquinazolin-6-ylcarbamate

HRID 1968630Notes

Reaction equation

HRID 1968630 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:21])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2].N1C=CC=CC=1.Cl[C:29]([O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:30]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([F:21])=[C:17]([NH:20][C:29](=[O:30])[O:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1)#[CH:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 59142793N4-(3-ethynylphenyl)-7-fluoroquinazoline-4,6-diamine

Product 1

HCID 59142774Phenyl 4-(3-ethynylphenylamino)-7-fluoroquinazolin-6-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

N4-(3-ethynylphenyl)-7-fluoroquinazoline-4,6-diamine (100 mg, 0.36 mmol) was dissolved into DMF (3 mL) containing pyridine (35 μL, 0.432 mmol). Phenyl chloroformate (46 μL, 0.36 mmol) was dropped into the mixture at room temperature and heated to 70° C. for 1 h to give phenyl 4-(3-ethynylphenylamino)-7-fluoroquinazolin-6-ylcarbamate. The obtained compound was used in the next step directly without purification. Then the amine (0.36 mmol) was added and stirred at 70° C. for 2.5 h. After cooled to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water. The combined organic layers were concentrated and purified with silica column to give Compound 60 (105 mg, 75% yield).

Sources & evidence

ORD record
ord-43bf74832b95476d965690ee6a8618cf
Source dataset
uspto-grants-2013_04
Patent number
US08426430B2

Reaction notes

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