Trifluoroacetic acid → (R)-N-(7-fluoro-1, 1-dimethyl-2,3-dihydro-1H-inden-5-yl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamide

HRID 2202239Notes

Reaction equation

HRID 2202239 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:10]=[C:11]([NH:20][C:21]([C@@H:23]2[N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30][C:29]3[N:28]=[C:27]([O:40][CH3:41])[CH:26]=[CH:25][C:24]2=3)=[O:22])[CH:12]=[C:13]2[C:17]=1[C:16]([CH3:19])([CH3:18])[CH2:15][CH2:14]2.C(=O)([O-])[O-].[K+].[K+]>C(=O)([O-])O.[Na+]>[F:8][C:9]1[CH:10]=[C:11]([NH:20][C:21]([C@@H:23]2[NH:32][CH2:31][CH2:30][C:29]3[N:28]=[C:27]([O:40][CH3:41])[CH:26]=[CH:25][C:24]2=3)=[O:22])[CH:12]=[C:13]2[C:17]=1[C:16]([CH3:18])([CH3:19])[CH2:15][CH2:14]2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 131735733tert-butyl (R)-5-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

Product 1

HCID 118622734(R)-N-(7-fluoro-1, 1-dimethyl-2,3-dihydro-1H-inden-5-yl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamideYield 97.1%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

TFA (13 mL) was added to tert-butyl (R)-5-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (957 mg, 2.04 mmol) at room temperature, and the mixture was stirred at room temperature for 20 min. The reaction mixture was poured into ice-cooled saturated aqueous sodium hydrogencarbonate solution (110 mL), and the pH of the mixture was adjusted to 8 with potassium carbonate. Then, the mixture was extracted with ethyl acetate (×3). The organic layer was washed with water and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give (R)—N-(7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine-5-carboxamide (732 mg, 1.981 mmol, 97%) as an off-white amorphous solid.

Workup

  1. additionThe reaction mixture was poured into ice-
  2. extractionThen, the mixture was extracted with ethyl acetate (×3)
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-69830b77a9034b72836541ee746f6234
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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