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 1496751ノート

反応式

HRID 1496751 の反応式
[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

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
70 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6baaac938de04e8bae9d0493f283bb12
出典データセット
uspto-grants-2015_12
特許番号
US09198917B2

反応ノート

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