Water → Methyl 5-(3,5-difluorophenylamino)pyrimido[4,5-c]quinoline-8-carboxylate
Reaction equation
Cl[C:2]1[C:11]2[N:12]=[CH:13][N:14]=[CH:15][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:16]([O:18][CH3:19])=[O:17])=[CH:5][C:4]=2[N:3]=1.[F:20][C:21]1[CH:22]=[C:23]([CH:25]=[C:26]([F:28])[CH:27]=1)[NH2:24].O>CN1C(=O)CCC1>[F:20][C:21]1[CH:22]=[C:23]([NH:24][C:2]2[C:11]3[N:12]=[CH:13][N:14]=[CH:15][C:10]=3[C:9]3[CH:8]=[CH:7][C:6]([C:16]([O:18][CH3:19])=[O:17])=[CH:5][C:4]=3[N:3]=2)[CH:25]=[C:26]([F:28])[CH:27]=1Participants
Conditions
- Temperature
- 120 °C
Procedure
methyl 5-chloropyrimido[4,5-c]quinoline-8-carboxylate (10 mg) was mixed with 3,5-difluoroaniline (100 mg) in NMP (0.1 ml). The mixture was heated under microwaves at 120° C. for 10 minutes. Water was added and the material extracted with CH2Cl2. The solvent was removed. Trituration in a mixture of ethylacetate and hexanes and filtration provided methyl 5-(3,5-difluorophenylamino)pyrimido[4,5-c]quinoline-8-carboxylate. This material was suspended in a 1:1 mixture of THF and MeOH (2 ml) and a 5N aqueous solution of Lithium Hydroxide was added. The mixture was vigorously stirred at room temperature for 5 hours. Water and 6N hydrochloric acid were added to induce precipitation of the expected material. The solid was filtered, washed with water, dried and suspended in MeOH. Filtration and drying gave 5-(3,5-difluorophenylamino)pyrimido[4,5-c]quinoline-8-carboxylic acid as a yellow solid (4 mg, 31% yield). LCMS (ES): 95% pure, m/z 353 [M+1]+. 1H NMR (DMSO-d6, 400 MHz) δ 6.90 (br t, J=9.6, 1H), 8.02 (dd, J=1.6, J=8.0, 1H), 8.18 (br d, J=10.8, 2H), 8.34 (d, J=1.6, 1H), 8.86 (d, J=8.4, 1H), 9.65 (s, 1H), 10.40 (s, 1H), 10.44 (s, 1H) ppm.
Workup
- extractionthe material extracted with CH2Cl2
- customThe solvent was removed
- additionTrituration in a mixture of ethylacetate and hexanes and filtration
Sources & evidence
- ORD record
- ord-d0b7c781d80e4658a630c15d88c94353
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09062043B2
Reaction notes
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