Acetone cardice → HCID 74221268, compound

HRID 928862Notes

Reaction equation

HRID 928862 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12](Cl)[C:11]([CH2:18][C:19]1[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=1)=[C:10]2[Cl:29].[CH3:30][N:31]1[C:35]([C:36]([C:38]2[CH:39]=[N:40][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:42][CH:43]=2)=[O:37])=[CH:34][N:33]=[CH:32]1.[C:48](=O)=[O:49].CC(C)=O>C1COCC1>[Cl:29][C:10]1[C:9]2[C:14](=[CH:15][CH:16]=[C:7]([C:36]([C:35]3[N:31]([CH3:30])[CH:32]=[N:33][CH:34]=3)([C:38]3[CH:39]=[N:40][C:41]([C:44]([F:47])([F:45])[F:46])=[CH:42][CH:43]=3)[OH:37])[CH:8]=2)[N:13]=[C:12]([O:49][CH3:48])[C:11]=1[CH2:18][C:19]1[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 18522661Acetone cardiceHCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone2×HCID 86715659HCID 86715659, compound2×HCID 178418339Butyllithium

Product 1

HCID 74221268HCID 74221268, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of n-BuLi (2.5 M in hexanes, 2.75 mL, 6.88 mmol) was added drop-wise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinolone (3.00 g, 6.95 mmol, Intermediate 65: step c) in dry THF (35 mL) in a dry ice-acetone bath. After 1.5 min, a solution of 1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (1.69 g, 6.61 mmol, Intermediate 36: step c) in dry THF (25 mL) was added drop-wise via syringe. An additional 10 mL of THF was used to complete the quantitative addition. The reaction mixture was stirred for 7 minutes in the dry ice-acetone bath, then placed into an ice-water bath. After 10 min, the ice-water bath was removed and the mixture was allowed to warm to ambient temperature. The reaction was quenched with saturated aqueous ammonium chloride and the mixture was partitioned between water and DCM. The layers were separated and the aqueous phase was further extracted with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 8.81 (d, J=2.1 Hz, 1H), 8.71 (d, J=2.1 Hz, 1H), 8.17 (d, J=2.1 Hz, 1H), 7.88 (ddd, J=8.3, 2.4, 0.9 Hz, 1H), 7.81 (d, J=8.8 Hz, 1H), 7.76 (ddd, J=8.2, 2.2, 1.0 Hz, 1H), 7.62 (dd, J=8.2, 0.9 Hz, 1H), 7.58-7.54 (m, 2H), 7.17-7.15 (m, 1H), 6.71 (s, 1H), 6.22 (d, J=1.2 Hz, 1H), 4.34 (s, 2H), 4.08 (s, 3H), 3.32 (s, 3H). MS m/e 608.0 (M+H).

Workup

  1. additionthe quantitative addition
  2. customplaced into an ice-water bath
  3. waitAfter 10 min
  4. customthe ice-water bath was removed
  5. customThe reaction was quenched with saturated aqueous ammonium chloride
  6. customthe mixture was partitioned between water and DCM
  7. customThe layers were separated
  8. extractionthe aqueous phase was further extracted with DCM
  9. dry with materialThe organic phase was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM)

Sources & evidence

ORD record
ord-0ab11b0542214180a8b51d343832b0b1
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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