Ethanol → N-(4-(2-Amino-6-methylpyrimidin-4-ylamino)phenyl)-4-(quinolin-4-ylamino)benzamide hydrochloride
Reaction equation
Cl.[NH2:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[N:18]=3)=[CH:12][CH:11]=2)=[O:8])=[CH:5][CH:4]=1.CO.CCO.[Cl:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[N:36]=[CH:35][CH:34]=1>[CH]Cl.O>[ClH:32].[NH2:24][C:19]1[N:18]=[C:17]([NH:16][C:13]2[CH:12]=[CH:11][C:10]([NH:9][C:7](=[O:8])[C:6]3[CH:25]=[CH:26][C:3]([NH:2][C:33]4[C:42]5[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=5)[N:36]=[CH:35][CH:34]=4)=[CH:4][CH:5]=3)=[CH:15][CH:14]=2)[CH:22]=[C:21]([CH3:23])[N:20]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To solution of amine E5 (267 mg, 0.720 mmol) in ˜1:1:1 MeOH:EtOH:H2O were sequentially added 4-chloroquinoline (1.06 g, 6.48 mmol) and 3 drops of cHCl, and the resulting mixture was refluxed for ˜24 h. After this time, solvent was removed under reduced pressure, and the resulting residue dried via two MeOH-azeotrope cycles. The residue was re-precipitated from MeOH/EtOAc, and then further purified by preparative HPLC, to afford Cpd. E as an amorphous yellow solid (16 mg, 4%). 1H NMR [(CD3)2SO]: 1.91 [s, 3H, ArCH3], 6.11 [s, 1H, ArH], 7.02 [d, J=6.77 Hz, 1H, ArH], 7.65 [d, J=8.55 Hz, 2H, ArH], 7.71 [br s, 2H, ArNH2], 7.84 [m, 4H, ArH], 8.04 [m, 2H, ArH], 8.15 [d, J=8.55 Hz, 2H, ArH], 8.63 [d, J=6.77 Hz, 1H, ArH], 8.70 [d, J=8.50 Hz, 1H, ArH], 10.38 [s, 2H, ArNHAr & ArH], 10.77 [br s, 1H, ArNHAr], 13.10 [v v br s, 2H, ArC(O)NHAr & quinoline-N+H]. LCMS (APCI+): 463 (100%). HPLC: 95.7%.
Workup
- temperaturethe resulting mixture was refluxed for ˜24 h
- customAfter this time, solvent was removed under reduced pressure
- dry with materialthe resulting residue dried via two MeOH-azeotrope cycles
- customThe residue was re-precipitated from MeOH/EtOAc
- customfurther purified by preparative HPLC
- customto afford Cpd
Sources & evidence
- ORD record
- ord-fe16af8b7d4140e2862560eb08231d61
- Source dataset
- uspto-grants-2011_05
- Patent number
- US07939546B2
Reaction notes
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