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

HRID 578678Notes

Reaction equation

HRID 578678 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. LCMS [540 (M+1)]. 1H NMR (400 MHz, DMSO-D6): 2.1875 (m, 1H), 2.3432 (m, 1H), 3.2379 (s, 3H), 3.3835 (m, 1H), 3.4522 (m, 1H), 5.7150 (m, 1H), 7.0524 (m, 2H), 7.2017 (m, 1H), 7.3317 (m, 1H), 7.6285 (m, 1H), 7.9371 (m, 6H), 8.0791 (m, 1H), 8.5544 (m, 1H), 8.6647 (s, 1H), 8.8136 (s, 1H), 10.3786 (s, 1H).

Workup

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

Sources & evidence

ORD record
ord-e81470ac603c4ce4ad74c614ffbd233c
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

Loading…