Trifluoroacetic acid → 5-cyclopropyl-N-[3-hydroxy-3-methyl-1-(methylamino)-1-oxobutan-2-yl]-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-2-carboxamide

HRID 1480302

Reaction equation

HRID 1480302 reaction equation
[OH:1][C:2]([CH3:17])([CH3:16])[CH:3]([NH:8][C:9](=[O:15])OC(C)(C)C)[C:4](=[O:7])[NH:5][CH3:6].FC(F)(F)C(O)=O.[CH:25]1([C:28]2[C:29]([O:37][C@@H:38]([CH3:43])[C:39]([F:42])([F:41])[F:40])=[CH:30][C:31](C(O)=O)=[N:32][CH:33]=2)[CH2:27][CH2:26]1>ClCCl>[CH:25]1([C:28]2[C:29]([O:37][C@@H:38]([CH3:43])[C:39]([F:42])([F:40])[F:41])=[CH:30][C:31]([C:9]([NH:8][CH:3]([C:2]([OH:1])([CH3:16])[CH3:17])[C:4]([NH:5][CH3:6])=[O:7])=[O:15])=[N:32][CH:33]=2)[CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 90203567HCID 90203567, compoundHCID 902045735-Cyclopropyl-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 902044565-cyclopropyl-N-[3-hydroxy-3-methyl-1-(methylamino)-1-oxobutan-2-yl]-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-[2-hydroxy-2-methyl-1-(methylcarbamoyl)propyl]carbamate (example 236a, 760 mg, 1.94 mmol) in dichloromethane (3 ml) was added trifluoroacetic acid (3.00 ml). The reaction mixture was stirred at room temperature overnight. The reaction mixture was evaporated down to dryness and the crude residue was dissolved in toluene. Volatiles were removed in vacuo to afford a white solid which was dried in HV overnight to yield the crude amine (680 mg) as a trifluroacetate salt which was used without any purification. The crude amine salt was used to synthesize the title compound in analogy to Example 112e, using 5-Cyclopropyl-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid (Example 68a) as starting materials and the title compound was isolated (76 mg, 59%); MS (ESI, m/z): 404.6 (M+H+).

Workup

  1. customThe reaction mixture was evaporated down to dryness
  2. dissolutionthe crude residue was dissolved in toluene
  3. customVolatiles were removed in vacuo
  4. customto afford a white solid which
  5. customwas dried in HV overnight
  6. customto yield the crude amine (680 mg) as a trifluroacetate salt which
  7. customwas used without any purification
  8. customto synthesize the title compound in analogy to Example 112e

Sources & evidence

ORD record
ord-4047267547494370a0941503eaa035ce
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Linked notes

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