Water → Methyl 3-(methylthio)-5-(phenylamino)pyrimido[4,5-c]quinoline-8-carboxylate

HRID 1919633Notes

Reaction equation

HRID 1919633 reaction equation
Cl[C:2]1[C:11]2[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:18]([O:20][CH3:21])=[O:19])=[CH:5][C:4]=2[N:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN1C(=O)CCC1>[CH3:17][S:16][C:13]1[N:14]=[CH:15][C:10]2[C:9]3[CH:8]=[CH:7][C:6]([C:18]([O:20][CH3:21])=[O:19])=[CH:5][C:4]=3[N:3]=[C:2]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:11]=2[N:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6115AnilineHCID 57500645Methyl 5-chloro-3-(methylthio)pyrimido[4,5-c]quinoline-8-carboxylate

Product 1

HCID 57500646Methyl 3-(methylthio)-5-(phenylamino)pyrimido[4,5-c]quinoline-8-carboxylate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

methyl 5-chloro-3-(methylthio)pyrimido[4,5-c]quinoline-8-carboxylate (1.0 eq, 182 mg, 0.57 mmol) was mixed with aniline (0.5 ml) in NMP (1 ml). The mixture was heated under microwave for 10 minutes at 120° C. Water was added and the resulting solid was filtered and dried. The compound was triturated in EtOAc and hexanes and filtered to afford methyl 3-(methylthio)-5-(phenylamino)pyrimido[4,5-c]quinoline-8-carboxylate as a yellow solid. LCMS (ES): >95% pure, m/z 377 [M+1]+. This material was suspended in CH2Cl2 (4 ml) and meta-chloroperbenzoic acid (77% pure, 2.5 eq, 165 mg, 0.737 mmol) was added in small portions. After one hour, an additional amount (100 mg) of mcpba was added and the mixture stirred for 1.5 hours. After addition of more CH2Cl2, the organic phase was washed with water (4×), dried over Na2SO4 and the solution was filtered through a pad of silica gel, eluting with a MeOH/CH2Cl2 mixture. After evaporation of the solvents, methyl 3-(methylsulfonyl)-5-(phenylamino)pyrimido[4,5-c]quinoline-8-carboxylate was isolated as a yellow solid (166 mg, 72% yield). LCMS (ES): >95% pure, m/z 409 [M+1]+, 1H NMR (DMSO-d6, 400 MHz) δ 3.77 (s, 3H), 3.93 (s, 3H), 7.15 (t, J=7.2, 1H), 7.45 (t, J=7.6, 2H), 7.99 (dd, J=2.0, J=8.4, 1H), 8.16 (d, J=7.6, 2H), 8.28 (d, J=2.0, 1H), 8.89 (d, J=8.8, 1H), 9.76 (s, 1H), 10.61 (s, 1H) ppm.

Workup

  1. filtrationthe resulting solid was filtered
  2. customdried
  3. customThe compound was triturated in EtOAc
  4. filtrationhexanes and filtered

Sources & evidence

ORD record
ord-83e1984d343640559454ddd728107ad9
Source dataset
uspto-grants-2012_05
Patent number
US08168651B2

Reaction notes

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