Water → HCID 86703612, compound

HRID 1849734Notes

Reaction equation

HRID 1849734 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:28]([C:29](O)([CH3:31])[CH3:30])=[CH:27][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:26][CH2:25][CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:33])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(N(S(F)(F)[F:40])CC)C.C(#N)C.O>ClCCl>[C:1]12([CH2:11][O:12][C:13]3[C:28]([C:29]([F:40])([CH3:30])[CH3:31])=[CH:27][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:26][CH2:25][CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:33])[CH:14]=3)[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2

Participants

6

Reactant 4

HCID 962WaterHCID 6342AcetonitrileHCID 123472(Diethylamino)sulfur trifluorideHCID 86703610HCID 86703610, compound

Product 1

HCID 86703612HCID 86703612, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-(2-hydroxypropan-2-yl)benzamide (0.067 g, 0.14 mmol) in anhydrous dichloromethane (10 mL) was added diethylaminosulfur trifluoride (22 μL, 0.17 mmol) at −78° C. The reaction mixture was stirred for 2 hours at −78° C. and then quenched by addition of saturated sodium bicarbonate solution (5 mL). The mixture was allowed to warm to ambient temperature and diluted with dichloromethane (50 mL). The organic phase was washed with brine (5 mL), dried over anhydrous magnesium sulfate, and filtered. The residue obtained after concentration of the filtrate in vacuo was purified by silica gel column chromatography using 0-20% ethyl acetate in hexanes as eluent to afford a beige solid. Lyophilization from acetonitrile and water (2 mL, 1:1) gave the title compound as colorless solid (0.012 g, 18%): 1H NMR (300 MHz, DMSO-d6) 11.74 (s, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.11 (d, J=12.7 Hz, 1H), 4.05 (t, J=7.6 Hz, 4H), 3.69 (s, 2H), 2.23-2.11 (m, 2H), 2.04-1.97 (m, 3H), 1.79-1.61 (m, 18H); 19F NMR (282 MHz, CDCl3) 6-109.8 (s, 1F), −130.0 (s, 1F); MS (ES−) m/z 481.2 (M−1).

Workup

  1. customquenched by addition of saturated sodium bicarbonate solution (5 mL)
  2. temperatureto warm to ambient temperature
  3. additiondiluted with dichloromethane (50 mL)
  4. washThe organic phase was washed with brine (5 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe residue obtained after concentration of the filtrate in vacuo
  8. customwas purified by silica gel column chromatography
  9. customto afford a beige solid

Sources & evidence

ORD record
ord-965f97b5e58041b9beccbab0b4abf2a5
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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