Trifluoroacetic acid → 4-(2-(1,2-dihydroxyethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528653Notes

Reaction equation

HRID 528653 reaction equation
[OH:1][CH:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([N:24](CC3C=CC(OC)=CC=3)[C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:23])=[O:22])[CH:19]=[CH:20][C:12]1=2)[CH2:3][OH:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:1][CH:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][O:14][C:13]2[CH:17]=[C:18]([S:21]([NH:24][C:25]3[S:26][CH:27]=[CH:28][N:29]=3)(=[O:22])=[O:23])[CH:19]=[CH:20][C:12]1=2)[CH2:3][OH:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 897617304-(2-(1,2-dihydroxyethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 897619534-(2-(1,2-dihydroxyethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 5.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-(1,2-dihydroxyethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (300 mg, 0.585 mmol) in DCM (5 mL) was added TFA (0.7 mL, Spectrochem) at 0° C. The reaction mixture was stirred at ambient temperature for 2 h. After completion, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (10 mL) and extracted with DCM (2×10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by prep HPLC to obtain 4-(2-(1,2-dihydroxyethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (14 mg, 5.9%) as a white solid. m/z (ESI) 434.0 (M+H)+. 1H NMR (400 MHz, DMSO) δ 12.48 (s, 1H), 7.61 (d, J=5.0 Hz, 1H), 7.37 (d, J=4.5 Hz, 2H), 7.23 (t, J=7.7 Hz, 1H), 7.16 (d, J=4.3 Hz, 1H), 7.11 (s, 1H), 7.05 (d, J=8.6 Hz, 1H), 6.71 (d, J=4.2 Hz, 1H), 6.05 (d, J=8.5 Hz, 1H), 5.16 (s, 1H), 4.66 (d, J=25.7 Hz, 2H), 4.34 (q, J=10.8, 10.3 Hz, 2H), 3.77 (t, J=8.3 Hz, 1H), 3.68-3.45 (m, 3H).

Workup

  1. customAfter completion, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (10 mL)
  2. extractionextracted with DCM (2×10 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude material which
  6. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-ae5ad0ea1a5844549f3b1904184686df
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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