Lithium diisopropylamide → 1-chloro-8-(pyrimidin-5-yl)-10H-chromeno[3,2-c]pyridin-10-one

HRID 1970265Notes

Reaction equation

HRID 1970265 reaction equation
C([N-]C(C)C)(C)C.[Li+].CCCCCCC.C1COCC1.[Cl:21][C:22]1[CH:27]=[C:26]([O:28][C:29]2[CH:41]=[CH:40][C:39]([C:42]3[CH:43]=[N:44][CH:45]=[N:46][CH:47]=3)=[CH:38][C:30]=2[C:31](N(CC)CC)=[O:32])[CH:25]=[CH:24][N:23]=1>C1COCC1>[Cl:21][C:22]1[C:27]2[C:31](=[O:32])[C:30]3[CH:38]=[C:39]([C:42]4[CH:47]=[N:46][CH:45]=[N:44][CH:43]=4)[CH:40]=[CH:41][C:29]=3[O:28][C:26]=2[CH:25]=[CH:24][N:23]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 21263495Tetrahydrofuran heptaneHCID 59272394HCID 59272394, compound

Product 1

HCID 592723441-chloro-8-(pyrimidin-5-yl)-10H-chromeno[3,2-c]pyridin-10-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Lithium diisopropylamide, 1.8 M in heptane/THF (5.80 mL, 10.45 mmol) was added dropwise to a −78° C. solution of 2-(2-chloropyridin-4-yloxy)-N,N-diethyl-5-(pyrimidin-5-yl)benzamide (1.000 g, 2.61 mmol) in THF (20.0 mL). The reaction mixture was stirred at −78° C. for 2.5 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and the mixture was partitioned between EtOAc and water. The aqueous phase was separated and extracted with DCM. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford an orange solid. This material was purified via column chromatography on silica gel (RediSep 40 g column, eluting with 100% EtOAc) to afford 1-chloro-8-(pyrimidin-5-yl)-10H-chromeno[3,2-c]pyridin-10-one as an off-white solid. MS m/z=310.0 [M+H]+. Calcd for C16H8ClN3O2: 309.7.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  2. customthe mixture was partitioned between EtOAc and water
  3. customThe aqueous phase was separated
  4. extractionextracted with DCM
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford an orange solid
  10. customThis material was purified via column chromatography on silica gel (RediSep 40 g column, eluting with 100% EtOAc)

Sources & evidence

ORD record
ord-23dae8265b2c450d97006b2206ffad7d
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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