Triethylamine → HCID 76284751, compound

HRID 1480200Notes

Reaction equation

HRID 1480200 reaction equation
[CH:1]1([C:4]2[C:5]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:6][C:7]([C:10]([NH:12][C:13]([CH3:22])([C:16]3[N:20]=[C:19]([CH3:21])[O:18][N:17]=3)[CH:14]=O)=[O:11])=[N:8][CH:9]=2)[CH2:3][CH2:2]1.Cl.[F:30][C:31]1([F:35])[CH2:34][NH:33][CH2:32]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH:1]1([C:4]2[C:5]([O:23][CH2:24][C:25]([F:26])([F:28])[F:27])=[CH:6][C:7]([C:10]([NH:12][C:13]([C:16]3[N:20]=[C:19]([CH3:21])[O:18][N:17]=3)([CH3:22])[CH2:14][N:33]3[CH2:34][C:31]([F:35])([F:30])[CH2:32]3)=[O:11])=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 90204216HCID 90204216, compound

Product 1

HCID 76284751HCID 76284751, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-cyclopropyl-N-[1-methyl-1-(5-methyl-1,2,4-oxadiazol-3-yl)-2-oxo-ethyl]-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide (example 128a, 0.075 g, 188 μmol) in dichloromethane (1 ml) was added 3,3-difluoroazetidine hydrochloride (26.8 mg, 207 μmol) and triethylamine (21.0 mg, 28.9 μl, 207 μmol). The reaction mixture was sonicated to completely dissolve solids and reaction mixture was then stirred at room temperature for 30 minutes, followed by addition of sodium triacetoxyborohydride (59.9 mg, 282 μmol). The reaction mixture was then stirred at room temperature overnight. The reaction was diluted with dichloromethane and extracted with a 2M aqueous solution of sodium carbonate. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (9.2 mg, 10%). MS (ESI, m/z): 476.5 (M+H+).

Workup

  1. customThe reaction mixture was sonicated to completely dissolve solids and reaction mixture
  2. stirringThe reaction mixture was then stirred at room temperature overnight
  3. extractionextracted with a 2M aqueous solution of sodium carbonate
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated down to dryness
  6. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-8d62d2a4a182429285002905135a6cd1
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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