1,8-Diazabicyclo(5.4.0)undec-7-ene → (4aR,6S,8aS)-8a-(2,4-difluorophenyl)-6-(2-methylpropyl)-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-2-amine

HRID 1775744노트

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HRID 1775744 반응식
N12CCCN=C1CCCCC2.[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C@:20]12[CH2:29][O:28][C@@H:27]([CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:26][C@H:25]1[CH2:24][S:23][C:22]([NH:34]C(=O)C1C=CC=CC=1)=[N:21]2>CO>[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C@:20]12[CH2:29][O:28][C@@H:27]([CH2:30][CH:31]([CH3:32])[CH3:33])[CH2:26][C@H:25]1[CH2:24][S:23][C:22]([NH2:34])=[N:21]2

참가 물질

4

반응물 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 90089508N-[(4aR,6S,8aS)-8a-(2,4-difluorophenyl)-6-(2-methylpropyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 73388368(4aR,6S,8aS)-8a-(2,4-difluorophenyl)-6-(2-methylpropyl)-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-2-amine

시약·촉매·용매 1

HCID 887Methanol용매

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온도
60 °C

실험 절차

1,8-Diazabicyclo[5.4.0]undec-7-ene (3.0 μL, 20 μmol) was added to a solution of N-[(4aR,6S,8aS)-8a-(2,4-difluorophenyl)-6-(2-methylpropyl)-4,4a, 5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C29) (10.5 mg, 23.6 μmol) in methanol (0.4 mL) and the reaction mixture was heated at 60° C. for 18 hours in a sealed vial. Solvent was removed under a stream of nitrogen, and the residue was partitioned between water (3 mL) and ethyl acetate (5 mL). The aqueous layer was extracted with ethyl acetate (5 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification was carried out via reversed phase high-performance liquid chromatography (Column: Waters XBridge C18, 5 μm; Mobile phase A: 0.03% ammonium hydroxide in water (v/v); Mobile phase B: 0.03% ammonium hydroxide in acetonitrile (v/v); Gradient: 30% to 100% B). Yield: 4.2 mg, 12 μmol, 51%. LCMS m/z 341.1 [M+H+]. 1H NMR (600 MHz, DMSO-d6) δ 7.31-7.36 (m, 1H), 7.15-7.20 (m, 1H), 7.08 (ddd, J=9, 8, 2 Hz, 1H), 3.86 (dd, J=10.5, 1.8 Hz, 1H), 3.54 (d, J=10.5 Hz, 1H), 3.50-3.56 (m, 1H), 2.62-2.73 (m, 3H), 1.71-1.79 (m, 1H), 1.52-1.60 (m, 1H), 1.45-1.50 (m, 1H), 1.40 (ddd, J=14, 8, 6 Hz, 1H), 1.21 (ddd, J=14, 8, 4.5 Hz, 1H), 0.89 (d, J=6.1 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H).

후처리

  1. customSolvent was removed under a stream of nitrogen
  2. customthe residue was partitioned between water (3 mL) and ethyl acetate (5 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (5 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification

출처 및 근거

ORD 기록
ord-dff0ac0c87eb431da1268ff0d43e4f02
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09260455B2

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