Trifluoroacetic acid → HCID 89761725, compound

HRID 528665Notes

Reaction equation

HRID 528665 reaction equation
[C:1]([CH2:3][O:4][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)#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([CH2:3][O:4][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)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89761966HCID 89761966, compound

Product 1

HCID 89761725HCID 89761725, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-(cyanomethoxy)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (200 mg, 0.364 mmol) in DCM (30 mL) was added TFA (0.5 mL) 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 (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude product which was purified by prep HPLC purification to obtain 4-(2-(cyanomethoxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a white solid (39 mg, 25%). MS (ESI, positive ion) m/z; 429.0 (M+1). 1H NMR (400 MHz, DMSO) δ 12.50 (s, 1H), 7.42-7.36 (m, 2H), 7.36-7.30 (m, 1H), 7.23-7.15 (m, 2H), 7.12 (d, J=2.0 Hz, 1H), 7.08 (dd, J=8.5, 2.1 Hz, 1H), 6.77 (d, J=4.5 Hz, 1H), 6.19 (d, J=8.5 Hz, 1H), 5.18 (s, 2H), 4.32 (t, J=4.2 Hz, 2H), 3.64 (t, J=4.2 Hz, 2H).

Workup

  1. customAfter completion, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution (20 mL)
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude product which
  6. customwas purified by prep HPLC purification

Sources & evidence

ORD record
ord-9fec7b0eedd947d28658429c30609c4b
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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