Water → Methyl 5-chloropyrimido(4,5-c)quinoline-8-carboxylate

HRID 1919628Notes

Reaction equation

HRID 1919628 reaction equation
O=[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[NH:3]1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:31].O>C1(C)C=CC=CC=1>[Cl:31][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

Participants

6

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 50942144Methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate

Product 1

HCID 50942242Methyl 5-chloropyrimido(4,5-c)quinoline-8-carboxylateYield 71.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

In a vial, methyl 5-oxo-5,6-dihydropyrimido[4,5-c]quinoline-8-carboxylate (1.0 eq, 151 mg, 0.59 mmol) was mixed in toluene (1 ml) with DIEA (1.5 eq, 155 ul, 0.89 mmol) and POCl3 (5 eq, 270 ul, 3.0 mmol). The mixture was stirred at 120° C. for 1 hour and cooled down to room temperature. After adding ice and water the compound was extracted with CH2Cl2 (4×). The solution was filtered over Na2SO4 and filtered through a pad of celite. After evaporation of the volatiles, the material was triturated in a mixture of ethyl acetate and hexanes, filtered and dried to afford methyl 5-chloropyrimido[4,5-c]quinoline-8-carboxylate as a light brown fluffy solid (115 mg, 71% yield). LCMS (ES): 95% pure, m/z 274 [M+1]+. 1H NMR (DMSO-d6, 400 MHz) δ 3.96 (s, 3H), 8.37 (dd, J=1.6, J=8.4, 1H), 8.60 (d, J=1.6, 1H), 9.15 (d, J=8.8, 1H), 9.74 (s, 1H), 10.61 (s, 1H) ppm

Workup

  1. temperaturecooled down to room temperature
  2. extractionwas extracted with CH2Cl2 (4×)
  3. filtrationThe solution was filtered over Na2SO4
  4. filtrationfiltered through a pad of celite
  5. customAfter evaporation of the volatiles
  6. customthe material was triturated in a mixture of ethyl acetate and hexanes
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-8ff5df54bd6044c2a1518b1d2ce7a538
Source dataset
uspto-grants-2012_05
Patent number
US08168651B2

Reaction notes

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