Lithium Hexamethyldisilazide → 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528559

Reaction equation

HRID 528559 reaction equation
Cl.[S:2]1[C:6]([NH2:7])=[CH:5][N:4]=[CH:3]1.[Br:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[N:19]1[CH2:24][CH2:23][O:22][C:21]2[CH:25]=[C:26]([S:29](Cl)(=[O:31])=[O:30])[CH:27]=[CH:28][C:20]1=2.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[CH:12]=[CH:11][C:10]=1[N:19]1[CH2:24][CH2:23][O:22][C:21]2[CH:25]=[C:26]([S:29]([NH:7][C:6]3[S:2][CH:3]=[N:4][CH:5]=3)(=[O:30])=[O:31])[CH:27]=[CH:28][C:20]1=2

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 467381465-Thiazolamine hydrochlorideHCID 897618504-(2-Bromo-4-(Trifluoromethyl)Phenyl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonyl Chloride2×

Product 1

HCID 897614214-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 25.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A flask containing thiazol-5-amine hydrochloride (0.093 g, 0.684 mmol), 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (INTERMEDIATE C, 0.284 g, 0.622 mmol), and THF (4.15 mL) was cooled to 0° C. LHMDS (1.0 M in THF) (1.866 mL, 1.866 mmol) was added dropwise and the reaction was stirred for 5 minutes at 0° C. The reaction was quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel column chromatography (40 g, gradient elution 0 to 100% EtOAc:Heptane) to afford 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.083 g, 0.160 mmol) as an orange oily solid. 1H NMR (400 MHz, DMSO-d6) δ=10.66 (s, 1 H), 8.69 (d, J=0.9 Hz, 1 H), 8.21 (d, J=1.6 Hz, 1 H), 7.91 (dd, J=1.5, 8.3 Hz, 1 H), 7.75 (d, J=7.8 Hz, 1 H), 7.35 (d, J=0.9 Hz, 1 H), 7.12 (d, J=2.2 Hz, 1 H), 7.05 (dd, J=2.2, 8.6 Hz, 1 H), 6.24 (d, J=8.6 Hz, 1 H), 4.37 (d, J=17.2 Hz, 2 H), 3.85-3.63 (m, 2 H). m/z (ESI) 520.2 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated ammonium chloride solution
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via silica gel column chromatography (40 g, gradient elution 0 to 100% EtOAc:Heptane)

Sources & evidence

ORD record
ord-f2e908305c824e7da4c8124ea46cdc90
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Linked notes

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