2,2-Difluoro-2-(fluorosulfonyl)acetic acid → (R)-4a-Difluoromethoxymethyl-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene

HRID 1907294노트

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HRID 1907294 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([CH2:21][OH:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:23]([C:26]2[CH:27]=[N:28][C:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:30][CH:31]=2)(=[O:25])=[O:24])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.FS([C:42]([F:47])([F:46])C(O)=O)(=O)=O>[Cu](I)I.C(#N)C>[F:46][CH:42]([F:47])[O:22][CH2:21][C@@:19]12[CH2:18][N:17]([S:23]([C:26]3[CH:27]=[N:28][C:29]([N:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)=[CH:30][CH:31]=3)(=[O:24])=[O:25])[CH2:16][CH2:15][C:14]1=[CH:13][C:12]1[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[CH:10][C:11]=1[CH2:20]2

참가 물질

5

반응물 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 66780233[(R)-1-(4-Fluorophenyl)-6-[[6-(4-morpholinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalen-4a-yl]methanol

생성물 1

HCID 56848978(R)-4a-Difluoromethoxymethyl-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene

시약·촉매·용매 2

HCID 83717Copper iodide촉매HCID 6342Acetonitrile용매

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온도
50 °C

실험 절차

A mixture of [(R)-1-(4-fluorophenyl)-6-[[6-(4-morpholinyl)-3-pyridinyl]sulfonyl]-1,4,7,8-tetrahydro-1,2,6-triazacyclopenta[b]naphthalen-4a-yl]methanol (0.21 g), copper iodide (0.0080 g) and acetonitrile under argon was treated with 2-(fluorosulfonyl)difluoroacetic acid (0.062 mL), and the resulting mixture was heated at 50° C. for 30 hours. The mixture was cooled to room temperature, partitioned between water and ethyl acetate and the aqueous phase extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 1:1 by volume), and then by preparative reverse-phase HPLC, eluting with a mixture of acetonitrile and water containing 0.1% formic acid (1:1 to 7:3 by volume) to afford the title compound as a white solid (0.021 g). LCMS (Method C): 576 (M+H)+, Retention time 11.6 minutes.

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between water and ethyl acetate
  3. extractionthe aqueous phase extracted with ethyl acetate
  4. dry with materialThe combined organic phase was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 1:1 by volume)
  8. washby preparative reverse-phase HPLC, eluting with a mixture of acetonitrile and water containing 0.1% formic acid (1:1 to 7:3 by volume)

출처 및 근거

ORD 기록
ord-0dfa600d94a7402cb4402b7aa72d558f
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598154B2

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