Hydrochloric Acid → 6-Amino-7-ethoxy-4-(3-ethynylphenylamino)quinoline-3-carbonitrile
Reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH2:17][CH3:18])=[C:9]([NH:12]C(=O)C)[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:19]#[N:20].[C:21]([C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=1)[NH2:26])#[CH:22].CS(O)(=O)=O.Cl>C(O)C>[NH2:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:16][CH2:17][CH3:18])[N:5]=[CH:4][C:3]([C:19]#[N:20])=[C:2]2[NH:26][C:25]1[CH:27]=[CH:28][CH:29]=[C:23]([C:21]#[CH:22])[CH:24]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
A mixture of N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide (23.2 g, 0.08 mol, 1.00 equiv), 3-ethynyl aniline (10.1 g, 0.094 mol, 1.18 equiv), methanesulfonic acid (2.3 ml, 0.0355 mol) in ethanol (60 0 ml) was stirred under refluxed for 6 hours and then 0.6N hydrogen chloride (1000 ml, 0.6 mol) was added. The reaction mixture was heated to 80° C. and held for 19 hours, and then cooled to 0° C. to form precipitate. The precipitate was filtered and added to a solution of 1N potassium carbonate (400 ml) in methanol (600 ml) in which the mixture was stirred for 3 hours. The reaction mixture was filtered, washed with 1:1 methanol/water (500 ml) and dried to give 21.3 g of product. MS (ESI) m/z: 563 (M+1).
Workup
- temperatureunder refluxed for 6 hours
- temperaturecooled to 0° C.
- customto form precipitate
- filtrationThe precipitate was filtered
- additionadded to a solution of 1N potassium carbonate (400 ml) in methanol (600 ml) in which the mixture
- stirringwas stirred for 3 hours
- filtrationThe reaction mixture was filtered
- washwashed with 1:1 methanol/water (500 ml)
- customdried
Sources & evidence
- ORD record
- ord-50316f8c2cd64fb5962c8ef1bad41e2c
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08748453B2
Reaction notes
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