8-Chloro-2-methyl-10-(trifluoromethyl)-pyrimido[5,4-b]quinolin-4(3H)-one → 10-Butyl-8-chloro-2-methyl-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-one

HRID 456980Notes

Reaction equation

HRID 456980 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[C:7]3[C:12](=[O:17])[NH:13][C:14]([CH3:16])=[N:15][C:6]3=[C:5]([C:18]([F:21])([F:20])[F:19])[C:4]=2[CH:3]=1.[Li][CH2:23][CH2:24][CH2:25][CH3:26]>C1COCC1.CN(CCN(C)C)C>[CH2:23]([C:5]1([C:18]([F:19])([F:21])[F:20])[C:4]2[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:9]=2[NH:8][C:7]2[C:12](=[O:17])[NH:13][C:14]([CH3:16])=[N:15][C:6]1=2)[CH2:24][CH2:25][CH3:26]

Participants

4

Reactant 2

HCID 1358136208-Chloro-2-methyl-10-(trifluoromethyl)-pyrimido[5,4-b]quinolin-4(3H)-oneHCID 178418339Butyllithium

Product 1

HCID 13548606010-Butyl-8-chloro-2-methyl-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-oneYield 17%

Reagents, catalysts & solvents 1

HCID 86588997Thf tmedaSolvent

Conditions

Temperature
-78 °C

Procedure

8-Chloro-2-methyl-10-(trifluoromethyl)-pyrimido[5,4-b]quinolin-4(3H)-one (13, 82 mg, 0.261 mmol) was suspended in THF-TMEDA (10:1, 1.74 mL) and cooled to −78° C. under a N2 atmosphere. n-BuLi was added dropwise and the reaction slowly became homogeneous. The reaction mixture was stirred at −78° C. for 20 minutes, then the ice bath was removed and the reaction allowed to warm to rt. After stirring for 90 min, the reaction was quenched with sat. aq. NH4Cl and was partitioned between EtOAc and H2O. The organic layer was separated and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated. Chromatography (SiO2, 60% EtOAc-hexane) provided the desired material 14 (17 mg, 17%). Rf 0.39 (50% EtOAc-hexane). 1H NMR (CDCl3, 300 MHz) δ 11.63 (br s, NH), 7.53 (s, 1H), 7.22 (dd, J=2.2, 8.4 Hz, 1H), 6.87 (br s, NH), 6.82 (d, J=8.4 Hz, 1H), 2.86 (m, 1H), 2.48 (s, 3H), 2.14 (m, 1H), 1.34 (m, 2H), 1.01 (m, 2H), 0.86 (t, J=7.3 Hz, 3H); 19F NMR (CDCl3, 300 MHz) δ−75.21. ESI-HRMS 372.1099 (M++H, C17H17ClON3F3 requires 372.1091).

Workup

  1. customthe reaction slowly became homogeneous
  2. customthe ice bath was removed
  3. temperatureto warm to rt
  4. stirringAfter stirring for 90 min
  5. customthe reaction was quenched with sat. aq. NH4Cl
  6. customwas partitioned between EtOAc and H2O
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with EtOAc (3×10 mL)
  9. washThe combined organics were washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-3c765f66de46415d9dee059a3741c082
Source dataset
uspto-grants-2007_03
Patent number
US07186830B2

Reaction notes

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