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

HRID 528649Notes

Reaction equation

HRID 528649 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH:12]([CH2:14][O:15][CH3:16])[O:11][C:10]3[CH:17]=[C:18]([S:21]([N:24](CC4C=CC(OC)=CC=4)[C:25]4[S:26][CH:27]=[CH:28][N:29]=4)(=[O:23])=[O:22])[CH:19]=[CH:20][C:9]2=3)=[C:4]([C:39]#[N:40])[CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH:12]([CH2:14][O:15][CH3:16])[O:11][C:10]3[CH:17]=[C:18]([S:21]([NH:24][C:25]4[S:26][CH:27]=[CH:28][N:29]=4)(=[O:22])=[O:23])[CH:19]=[CH:20][C:9]2=3)=[C:4]([C:39]#[N:40])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 897619324-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 897616784-(4-chloro-2-cyanophenyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 52.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (170 mg, 0.28 mmol) in dichloromethane (10 mL) was added trifluroacetic acid (0.7 mL, Spectrochem) at 0° C. and the mixture was allowed to stir at room temperature for 4 h. The volatiles were removed under reduced pressure and the residue was basified (pH˜10) with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to get the crude material which was further purified by column chromatography (silica gel 100-200 mesh, 0-2% methanol in dichloromethane) to obtain 4-(4-chloro-2-cyanophenyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (70 mg, 51.5%) as an off white solid. m/z (ESI) 476.8 (M+H)+. 1H NMR (400 MHz, DMSO) δ 12.71 (s, 1H), 8.13 (d, J=2.5 Hz, 1H), 7.84 (dd, J=8.8, 2.5 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.35-7.04 (m, 3H), 6.80 (d, J=4.6 Hz, 1H), 6.57 (d, J=8.5 Hz, 1H), 4.46 (d, J=4.6 Hz, 1H), 3.80-3.76 (m, 1H), 3.65-3.57 (m, 3H), 3.29 (s, 3H).

Workup

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

Sources & evidence

ORD record
ord-41e3470c58c3479792c7e612065c5260
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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