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

HRID 2204239ノート

反応式

HRID 2204239 の反応式
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]

参加物

7

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-be62f4e3364b48809a351ddcee98fd8a
出典データセット
uspto-grants-2016_06
特許番号
US09365588B2

反応ノート

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