Phosphorus oxychloride → Methyl 5-chloro-3-(methylthio)pyrimido[4,5-c]quinoline-8-carboxylate

HRID 604357Notes

Reaction equation

HRID 604357 reaction equation
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[NH:9][C:8](=O)[C:7]=2[N:21]=1.O=P(Cl)(Cl)[Cl:24].CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[Cl:24][C:8]1[C:7]2[N:21]=[C:3]([S:2][CH3:1])[N:4]=[CH:5][C:6]=2[C:15]2[CH:14]=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=2[N:9]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 57500644Methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate

Product 1

HCID 57500645Methyl 5-chloro-3-(methylthio)pyrimido[4,5-c]quinoline-8-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

Methyl 3-(methylthio)-5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (1.0 eq, 279 mg, 0.926 mmol) was suspended in toluene (2 ml). POCl3 (2 ml) and DIEA (0.5 ml) were added and the mixture stirred at 120° C. for 5 hours. The volatiles were removed in vacuo and CH2Cl2 was added. The organic phase was washed with saturated aqueous sodium bicarbonate, washed with water and dried over Na2SO4. The solution was filtered through a pad of celite and the solvents removed in vacuo. The material was triturated in hexanes and AcOEt, filtered and dried to provide methyl 5-chloro-3-(methylthio)pyrimido[4,5-c]quinoline-8-carboxylate as a beige solid (184 mg, 63% yield). LCMS (ES): >95% pure, m/z 320 [M+1]+, 322 [M+3]+.

Workup

  1. customThe volatiles were removed in vacuo and CH2Cl2
  2. additionwas added
  3. washThe organic phase was washed with saturated aqueous sodium bicarbonate
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered through a pad of celite
  7. customthe solvents removed in vacuo
  8. customThe material was triturated in hexanes
  9. filtrationAcOEt, filtered
  10. customdried

Sources & evidence

ORD record
ord-79be95b5a6b440f78c6e14fb8a285a9d
Source dataset
uspto-grants-2011_03
Patent number
US07910600B2

Reaction notes

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