Hydrochloric Acid → HCID 117761114, 화합물

HRID 523271

반응식

HRID 523271 반응식
[Br:1][C:2]1[C:3]([Cl:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C[Al](C)C.[F:14][C:15]1[C:20]2[NH:21]C(=O)[O:23][C:24](=O)[C:19]=2[CH:18]=[CH:17][CH:16]=1.Cl>C1(C)C=CC=CC=1>[NH2:21][C:20]1[C:15]([F:14])=[CH:16][CH:17]=[CH:18][C:19]=1[C:24]([NH:5][C:4]1[CH:6]=[CH:7][CH:8]=[C:2]([Br:1])[C:3]=1[Cl:9])=[O:23]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 189585Benzenamine, ar-bromo-ar-chloro-HCID 105353933-Fluoroisatoic anhydrideHCID 16682925Trimethylaluminum

생성물 1

HCID 117761114HCID 117761114, 화합물수율 35%

시약·촉매·용매 1

HCID 1140Toluene용매2회

실험 절차

A mixture of 3-bromo-2-chloroaniline [prepared according to the procedure described in U.S. Pat. No. 8,242,260] (600 mg, 2.91 mmol) and toluene (10 mL) was cooled to 0° C. and slowly treated with 2 M trimethylaluminum in toluene (2.47 mL, 4.94 mmol). The mixture was allowed to warm to room temperature and stirred for 15 min. The mixture was treated with 8-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (684 mg, 3.78 mmol) and heated at 50° C. for 16 h. The mixture was cooled to 0° C. and treated dropwise with 1M aqueous HCl until gas evolution stopped, and stirred for 2 h while allowing to warm to room temperature. The mixture was extracted three times with EtOAc. The combined organic phases were washed sequentially with saturated aqueous NaHCO3 and brine, dried and concentrated. The residue was purified by column chromatography on silica gel (24 g), eluting with EtOAc-hexanes (gradient from 0-30%), to provide 2-amino-N-(3-bromo-2-chlorophenyl)-3-fluorobenzamide as a pale yellow solid (350 mg, 35% yield). Mass spectrum m/z 343, 345 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 8.46 (dd, J=8.4, 1.3 Hz, 1H), 8.42 (br. s., 1H), 7.43 (dd, J=8.0, 1.4 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.22 (t, J=8.3 Hz, 1H), 7.15 (ddd, J=11.0, 8.0, 1.2 Hz, 1H), 6.69 (td, J=8.0, 5.1 Hz, 1H), 5.72 (br. s., 2H).

후처리

  1. customprepared
  2. temperatureheated at 50° C. for 16 h
  3. temperatureThe mixture was cooled to 0° C.
  4. stirringstirred for 2 h
  5. temperatureto warm to room temperature
  6. extractionThe mixture was extracted three times with EtOAc
  7. washThe combined organic phases were washed sequentially with saturated aqueous NaHCO3 and brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel (24 g)
  11. washeluting with EtOAc-hexanes (gradient from 0-30%)

출처 및 근거

ORD 기록
ord-3802b80f12224e709ce45a0b0b375dbe
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334290B2

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