Trifluoroacetic acid → HCID 89761393, compound

HRID 528579Notes

Reaction equation

HRID 528579 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[N:13]1[CH:18]([CH3:19])[CH2:17][O:16][C:15]2[CH:20]=[C:21]([S:24]([N:27](CC3C=CC(OC)=CC=3)[C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:26])=[O:25])[CH:22]=[CH:23][C:14]1=2)#[N:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>ClCCl>[C:1]([C:3]1[CH:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:6]=[CH:5][C:4]=1[N:13]1[CH:18]([CH3:19])[CH2:17][O:16][C:15]2[CH:20]=[C:21]([S:24]([NH:27][C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:25])=[O:26])[CH:22]=[CH:23][C:14]1=2)#[N:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 897616224-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 89761393HCID 89761393, compoundYield 84.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (790 mg, 1.31 mmol) in dichloromethane (20 mL) was added TFA (2.0 mL, Spectrochem) at 0° C. and the mixture was allowed to stir at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to get the crude material which was basified (pH˜9) with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to get the crude material which was purified by column chromatography (silica gel 100-200 mesh, elution 0-5% methanol in dichloromethane) to obtain 4-(2-cyano-4-(trifluoromethyl)phenyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (530 mg, 84%) as off white solid. 1H NMR (400 MHz, DMSO) δ 12.66 (s, 1H), 8.44 (s, 1H), 8.08 (d, J=7.5 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.27-7.22 (m, 2H), 7.19 (d, J=8.5 Hz, 1H), 6.82 (d, J=4.5 Hz, 1H), 6.64 (d, J=8.5 Hz, 1H), 4.28-4.03 (m, 3H), 1.20 (d, J=6.5 Hz, 3H); MS (ESI, positive ion) m/z 481.1 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto get the crude material which
  3. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto get the crude material which
  8. customwas purified by column chromatography (silica gel 100-200 mesh, elution 0-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-01080d1586154c37a9ce5b5b00ea7010
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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