1,2-Dichloroethane → (4-Fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone

HRID 2204248노트

반응식

HRID 2204248 반응식
[CH:1]1[N:9]2[C:4]([C:5]3([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[O:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)=[CH:3][CH:2]=1.[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][C:21]=1[S:29]([CH3:32])(=[O:31])=[O:30].C(N(CC)CC)C.C(Cl)CCl>ClCCl>[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([N:16]2[CH2:17][CH2:18][C:5]3([C:4]4=[CH:3][CH:2]=[CH:1][N:9]4[C:8]4[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=4[O:6]3)[CH2:14][CH2:15]2)=[O:25])=[CH:22][C:21]=1[S:29]([CH3:32])(=[O:30])=[O:31]

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 106803154-Fluoro-3-(methylsulphonyl)benzoic acidHCID 58550727Spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]

생성물 1

HCID 58551140(4-Fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone수율 54.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (257 mg, 0.928 mmol), 4-fluoro-3-methylsulfonyl-benzoic acid (203 mg, 0.928 mmol), triethylamine (518 μL, 3.71 mmol), and EDC (196 mg, 1.02 mmol) were combined in dichloromethane (10 mL) and the reaction mixture was stirred at room temperature for 4 d. The reaction mixture was washed three times with a 1M solution of hydrochloric acid, followed by three washes with a saturated aqueous solution of sodium bicarbonate, followed by three washes of a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to yield the crude product. The crude material was purified column chromatography utilizing a gradient of 0-75% ethyl acetate in hexanes to yield (4-fluoro-3-methylsulfonyl-phenyl)-spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl-methanone (222 mg, 54%) as a colorless oil. ESI-MS m/z calc. 440.1, found 441.1 (M+1)+; Retention time: 1.51 minutes (3 min run).

후처리

  1. washThe reaction mixture was washed three times with a 1M solution of hydrochloric acid
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customto yield the crude product
  6. customThe crude material was purified column chromatography

출처 및 근거

ORD 기록
ord-cf8bd86b2ab9424a90b8f8106704bb3c
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365588B2

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