(Diethylamino)sulfur trifluoride → 5-(1-fluorocyclobutyl)-N-[2-(5-methyl-1,2,4-oxadiazol-3-yl)-1-methylsulfonylpropan-2-yl]-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-2-carboxamide

HRID 1480203Notes

Reaction equation

HRID 1480203 reaction equation
O[C:2]1([C:6]2[C:7]([O:28][C@@H:29]([CH3:34])[C:30]([F:33])([F:32])[F:31])=[CH:8][C:9]([C:12]([NH:14][C:15]([C:22]3[N:26]=[C:25]([CH3:27])[O:24][N:23]=3)([CH3:21])[CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])=[O:13])=[N:10][CH:11]=2)[CH2:5][CH2:4][CH2:3]1.CCN(S(F)(F)[F:41])CC>ClCCl>[F:41][C:2]1([C:6]2[C:7]([O:28][C@@H:29]([CH3:34])[C:30]([F:31])([F:32])[F:33])=[CH:8][C:9]([C:12]([NH:14][C:15]([C:22]3[N:26]=[C:25]([CH3:27])[O:24][N:23]=3)([CH3:21])[CH2:16][S:17]([CH3:20])(=[O:18])=[O:19])=[O:13])=[N:10][CH:11]=2)[CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 902034235-(1-hydroxycyclobutyl)-N-[1-methyl-1-(5-methyl-1,2,4-oxadiazol-3-yl)-2-methylsulfonyl-ethyl]-4-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-2-carboxamide

Product 1

HCID 902043215-(1-fluorocyclobutyl)-N-[2-(5-methyl-1,2,4-oxadiazol-3-yl)-1-methylsulfonylpropan-2-yl]-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-2-carboxamideYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(1-hydroxycyclobutyl)-N-[2-(5-methyl-1,2,4-oxadiazol-3-yl)-1-methylsulfonylpropan-2-yl]-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-2-carboxamide (example 126e, 21 mg, 41.5 μmol) in dry dichloromethane (200 μl) under an argon atmosphere cooled down to 0° C. was added DAST (10.0 mg, 8.22 μl, 62.2 μmol). The reaction mixture was stirred at 0° C. for 1 h and quenched by addition of a 2M aqueous solution of sodium carbonate. The bi-phasic mixture was stirred for 15 minutes and the organic phase was collected. The organic phase was evaporated down to dryness and the crude material was purified by preparative HPLC to yield the title compound (9.2 mg, 44%). MS (ESI, m/z): 509.5 (M+H+).

Workup

  1. customquenched by addition of a 2M aqueous solution of sodium carbonate
  2. stirringThe bi-phasic mixture was stirred for 15 minutes
  3. customthe organic phase was collected
  4. customThe organic phase was evaporated down to dryness
  5. customthe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-6ebcf35676fb46f08d6d1acf35091b32
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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