4-(Trifluoromethoxy)benzoic acid → 4-{3-Methoxy-1-[3-(4-trifluoromethoxy-benzoylamino)-phenyl]-propylamino}-quinazoline-8-carboxylic acid amide

HRID 474442Notes

Reaction equation

HRID 474442 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]([NH:13][C:14]2[C:23]3[C:18](=[C:19]([C:24]([NH2:26])=[O:25])[CH:20]=[CH:21][CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:10][O:11][CH3:12])[CH:5]=[CH:6][CH:7]=1.Cl.CN(C)CCCN=C=NCC.N1(O)C2C=CC=CC=2N=N1.[F:49][C:50]([F:62])([F:61])[O:51][C:52]1[CH:60]=[CH:59][C:55]([C:56](O)=[O:57])=[CH:54][CH:53]=1.C(N(C(C)C)C(C)C)C>CN(C=O)C>[CH3:12][O:11][CH2:10][CH2:9][CH:8]([NH:13][C:14]1[C:23]2[C:18](=[C:19]([C:24]([NH2:26])=[O:25])[CH:20]=[CH:21][CH:22]=2)[N:17]=[CH:16][N:15]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:56](=[O:57])[C:55]2[CH:59]=[CH:60][C:52]([O:51][C:50]([F:49])([F:61])[F:62])=[CH:53][CH:54]=2)[CH:3]=1

Participants

7

Reactant 5

HCID 676134-(Trifluoromethoxy)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667632604-{[1-(3-Aminophenyl)-3-methoxypropyl]amino}quinazoline-8-carboxamide

Product 1

HCID 667635194-{3-Methoxy-1-[3-(4-trifluoromethoxy-benzoylamino)-phenyl]-propylamino}-quinazoline-8-carboxylic acid amideYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-{[1-(3-aminophenyl)-3-methoxypropyl]amino}quinazoline-8-carboxamide (50.00 mg; 0.14 mmol; 1.00 eq.), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (30 mg; 0.16 mmol; 1.10 eq.) and 1H-1,2,3-benzotriazol-1-ol (22 mg; 0.16 mmol; 1.10 eq.) in dry DMF (1 mL) were added 4-(trifluoromethoxy)benzoic acid (33 mg; 0.16 mmol; 1.10 eq.) and N-ethyl-N-isopropylpropan-2-amine (0.08 ml; 0.43 mmol; 3.00 eq.). The mixture was stirred overnight. After concentration, the crude was purified by reverse phase HPLC to obtain 26 mg of the title product in 34% yield.

Workup

  1. concentrationAfter concentration
  2. customthe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-747ad69301ec48709680cb4b3da69e8c
Source dataset
uspto-grants-2014_01
Patent number
US08637532B2

Reaction notes

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