Triethylamine → N-[(4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 1496751노트

반응식

HRID 1496751 반응식
[NH2:1][CH2:2][C:3]1[C:4]([F:31])=[CH:5][C:6]([F:30])=[C:7]([C@:9]23[CH2:18][O:17][C@@H:16]([CH2:19][F:20])[CH2:15][C@H:14]2[CH2:13][S:12][C:11]([NH:21][C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:10]3)[CH:8]=1.C(N(CC)CC)C.FC(F)(F)S(O[CH2:45][C:46]([F:49])([F:48])[F:47])(=O)=O>C(#N)C>[F:30][C:6]1[CH:5]=[C:4]([F:31])[C:3]([CH2:2][NH:1][CH2:45][C:46]([F:49])([F:48])[F:47])=[CH:8][C:7]=1[C@:9]12[CH2:18][O:17][C@@H:16]([CH2:19][F:20])[CH2:15][C@H:14]1[CH2:13][S:12][C:11]([NH:21][C:22](=[O:29])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)=[N:10]2

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 86762645N-[(4aR,6R,8aS)-8a-[5-(aminomethyl)-2,4-difluorophenyl]-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 86762647N-[(4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
70 °C

실험 절차

A solution of N-[(4aR,6R,8aS)-8a-[5-(aminomethyl)-2,4-difluorophenyl]-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C26) (0.598 g, 1.33 mmol) in acetonitrile (13 mL) was treated with triethylamine (0.277 mL, 2.00 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.288 mL, 2.00 mmol). The reaction vial was sealed and the resulting solution was stirred at 70° C. for 16 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to yield a brown solid. The solid was partitioned between water (100 mL) and ethyl acetate (100 mL). The organics were isolated and the aqueous layer was extracted further with ethyl acetate (2×50 mL). The combined organics were then washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification via silica gel chromatography (Gradient: 0% to 60% ethyl acetate in heptane) afforded the product as a white solid. Yield: 0.4064 g, 57%. LCMS m/z 532.0 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.12 (br d, J=8 Hz, 2H), 7.45-7.59 (m, 3H), 7.08 (dd, J=12.3, 9.6 Hz, 1H), 4.50-4.52 (m, 1H), 4.38-4.40 (m, 1H), 4.15 (dd, J=12.1, 2 Hz, 1H), 3.90-3.94 (m, 3H), 3.00 (dd, J=13.4, 4.0 Hz, 1H), 2.77 (dd, J=13.1, 2.9 Hz, 1H), 1.87-1.96 (m, 1H), 1.69-1.72 (m, 1H).

후처리

  1. customThe reaction vial was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customto yield a brown solid
  5. customThe solid was partitioned between water (100 mL) and ethyl acetate (100 mL)
  6. customThe organics were isolated
  7. extractionthe aqueous layer was extracted further with ethyl acetate (2×50 mL)
  8. washThe combined organics were then washed with brine (100 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurification via silica gel chromatography (Gradient: 0% to 60% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-6baaac938de04e8bae9d0493f283bb12
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09198917B2

반응 노트

불러오는 중…