Isopropanol → HCID 118036667, compound

HRID 1777877Notes

Reaction equation

HRID 1777877 reaction equation
[CH3:1][CH:2]([OH:4])[CH3:3].[H-].[Na+].[C:7]([C:9]1[C:10](F)=[CH:11][C:12]([NH:15][C:16]([N:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH:28]([O:31][CH3:32])[O:29][CH3:30])[N:26]=3)[CH2:21][CH2:20][CH2:19]2)=[O:17])=[N:13][CH:14]=1)#[N:8]>CC(N(C)C)=O.CCOC(C)=O>[C:7]([C:9]1[C:10]([O:4][CH:2]([CH3:3])[CH3:1])=[CH:11][C:12]([NH:15][C:16]([N:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH:28]([O:31][CH3:32])[O:29][CH3:30])[N:26]=3)[CH2:21][CH2:20][CH2:19]2)=[O:17])=[N:13][CH:14]=1)#[N:8]

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 118036851HCID 118036851, compound2×

Product 1

HCID 118036667HCID 118036667, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent2×

Procedure

2-Propanol (16.2 mg, 0.269 mmol) was diluted in DMA (1 ml) under argon and treated with NaH (60% dispersion in mineral oil, 10.77 mg, 0.269 mmol). The reaction mixture was stirred for 30 min at room temperature. This mixture was added to a solution of N-(5-cyano-4-fluoropyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 33, 25 mg, 0.054 mmol) in DMA (1 ml). The reaction mixture was then stirred at room temperature for 1 h and the at 110° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with EtOAc, washed with sat. aq. NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated to give the title compound as a white solid. (UPLC-MS 3) tR 1.27 min; ESI-MS 412.2 [M+H]+.

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for 1 h
  2. waitthe at 110° C. for 4 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washwashed with sat. aq. NaHCO3, water and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)
  9. additionThe product containing fractions
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-998041c6d9ec46968d31b40517cd67d8
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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