Triethylamine → (4-Tert-butylsulfonylphenyl)-[1'-(trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone

HRID 2204238노트

반응식

HRID 2204238 반응식
[F:1][C:2]([F:22])([F:21])[C:3]1[N:11]2[C:6]([C:7]3([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=32)=[CH:5][CH:4]=1.[C:23]([S:27]([C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=1)(=[O:29])=[O:28])([CH3:26])([CH3:25])[CH3:24].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>ClCCl>[C:23]([S:27]([C:30]1[CH:31]=[CH:32][C:33]([C:34]([N:18]2[CH2:17][CH2:16][C:7]3([C:6]4=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:21])[F:22])[N:11]4[C:10]4[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=4[O:8]3)[CH2:20][CH2:19]2)=[O:35])=[CH:37][CH:38]=1)(=[O:29])=[O:28])([CH3:26])([CH3:25])[CH3:24]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596775524-(tert-Butylsulfonyl)benzoic acidHCID 674640241'-(Trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]

생성물 1

HCID 58551655(4-Tert-butylsulfonylphenyl)-[1'-(trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone수율 16.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

1′-(Trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (172 mg, 0.559 mmol), 4-tert-butylsulfonylbenzoic acid (176 mg, 0.727 mmol), 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (150 mg, 0.783 mmol), and triethylamine (312 μL, 2.24 mmol) were combined in dichloromethane (3.4 mL). The reaction mixture was allowed to stir for 72 hours at room temperature. 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 by reverse phase preparative chromatography utilizing a gradient of 10-99% acetonitrile in water to yield (4-tert-butylsulfonylphenyl)-[1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone (49 mg, 16%) as a white solid. ESI-MS m/z calc. 532.2, found 533.5 (M+1)+. Retention time: 2.10 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.89 (d, J=8.0 Hz, 2H), 7.73 (d, J=8.0 Hz, 2H), 7.57 (d, J=8.0 Hz, 1H), 7.35-7.25 (m, 2H), 7.25-7.16 (m, 1H), 7.03 (d, J=3.9 Hz, 1H), 6.40 (d, J=3.9 Hz, 1H), 4.53-4.37 (m, 1H), 3.57-3.14 (m, 3H), 2.17-1.78 (m, 4H), 1.26 (s, 9H).

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 by reverse phase preparative chromatography

출처 및 근거

ORD 기록
ord-692eee9b6138482b90edfa5d6835dd43
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365588B2

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