Acetic Acid → 6-{5-[2-(tert-Butyl-dimethyl-silanyloxy)-ethylamino]-pyridin-3-yl}-1-methyl-3,4-dihydro-1H-quinolin-2-one

HRID 1774786Notes

Reaction equation

HRID 1774786 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1.CC(O)=O.[Si:25]([O:32][CH2:33][CH:34]=O)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].[BH3-]C#N.[Na+].C([O-])(O)=O.[Na+]>CO.C1COCC1.CCOC(C)=O>[C:28]([Si:25]([CH3:27])([CH3:26])[O:32][CH2:33][CH2:34][NH:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 866791056-(5-Amino-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride

Product 1

HCID 866791516-{5-[2-(tert-Butyl-dimethyl-silanyloxy)-ethylamino]-pyridin-3-yl}-1-methyl-3,4-dihydro-1H-quinolin-2-oneYield 68.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(5-amino-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride (intermediate A-2, 0.062 g, 0.214 mmol) in MeOH (1.5 mL) was added AcOH (0.154 g, 2.57 mmol), followed by 2-(tert-butyldimethylsilyloxy)acetaldehyde (0.039 g, 0.225 mmol) and the reaction mixture was stirred at room temperature for 1 h. Then, NaBH3CN (0.027 g, 0.428 mmol) in THF (0.6 mL) was added to the reaction mixture and stirring at room temperature was continued for 2 h. The mixture was diluted with EtOAc, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with EtOAc (2×25 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.06 g, 68%) as a yellow solid. MS: 412.3 (M+H+).

Workup

  1. stirringstirring at room temperature
  2. waitwas continued for 2 h
  3. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
  4. washCombined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was purified by silica gel flash chromatography
  9. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-ea05bff66aad4b96827f18469f20fa17
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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