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

HRID 2204239노트

반응식

HRID 2204239 반응식
CN1CCOCC1.[F:8][C:9]([F:29])([F:28])[C:10]1[N:18]2[C:13]([C:14]3([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=32)=[CH:12][CH:11]=1.[C:30]([S:34]([C:36]1[CH:44]=[CH:43][C:39]([C:40](O)=[O:41])=[CH:38][CH:37]=1)=[O:35])([CH3:33])([CH3:32])[CH3:31].CCN=C=NCCCN(C)C.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[C:30]([S:34]([C:36]1[CH:37]=[CH:38][C:39]([C:40]([N:25]2[CH2:24][CH2:23][C:14]3([C:13]4=[CH:12][CH:11]=[C:10]([C:9]([F:8])([F:28])[F:29])[N:18]4[C:17]4[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=4[O:15]3)[CH2:27][CH2:26]2)=[O:41])=[CH:43][CH:44]=1)=[O:35])([CH3:33])([CH3:31])[CH3:32]

참가 물질

7

반응물 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 674640241'-(Trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]HCID 89543041HCID 89543041, 화합물

생성물 1

HCID 71571932(4-Tert-butylsulfinylphenyl)-[1'-(trifluoromethyl)spiro-[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone수율 45.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

4-methyl morpholine (1.96 mL, 17.8 mmol) was added to a mixture of 1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (1.45 g, 3.56 mmol), 4-tert-butylsulfinylbenzoic acid (807 mg, 3.56 mmol), EDCI (1.03 g, 5.35 mmol), 1-hydroxybenzotriazole (723 mg, 5.35 mmol) and DMF (14.5 mL) at room temperature. The mixture was heated at 50° C. overnight before it was cooled to room temperature and partitioned between ethyl acetate and 1N HCl. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (0-30% ethyl acetate/CH2Cl2, then 0-100% ethyl acetate/hexanes) to provide (4-tert-butylsulfinylphenyl)-[1′-(trifluoromethyl)spiro-[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone (831 mg, 44%) as a white solid. 1H NMR (400 MHz, DMSO) δ 7.68-7.62 (m, 4H), 7.57 (d, J=8.1 Hz, 1H), 7.33-7.26 (m, 2H), 7.24-7.17 (m, 1H), 7.02 (d, J=4.0 Hz, 1H), 6.41 (d, J=4.0 Hz, 1H), 4.52-4.37 (m, 1H), 3.49 (s, 2H), 3.26-3.13 (m, 1H), 2.16-1.96 (m, 3H), 1.96-1.80 (m, 1H), 1.09 (s, 9H). ESI-MS m/z calc. 516.2, found 517.2 (M+1)+; Retention time: 1.94 minutes (3 min run).

후처리

  1. temperaturewas cooled to room temperature
  2. custompartitioned between ethyl acetate and 1N HCl
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (0-30% ethyl acetate/CH2Cl2

출처 및 근거

ORD 기록
ord-be62f4e3364b48809a351ddcee98fd8a
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365588B2

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