Cesium carbonate → HCID 86680517、化合物

HRID 1184601ノート

反応式

HRID 1184601 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=1.[CH:12]1([C:15]2[N:16]=[CH:17][C:18]([O:21][CH:22]3[CH2:31][N:25]4[CH2:26][CH2:27][NH:28][C:29](=[O:30])[CH:24]4[CH2:23]3)=[N:19][CH:20]=2)[CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:12]1([C:15]2[N:16]=[CH:17][C:18]([O:21][C@H:22]3[CH2:31][N:25]4[CH2:26][CH2:27][N:28]([C:2]5[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=5)[C:29](=[O:30])[C@@H:24]4[CH2:23]3)=[N:19][CH:20]=2)[CH2:14][CH2:13]1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27829022-Bromo-6-(trifluoromethyl)pyridineHCID 86680516HCID 86680516、化合物

生成物 1

HCID 86680517HCID 86680517、化合物収率 17.66%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
110 °C

実験手順

A 4 mL vial was charged with 2-bromo-6-(trifluoromethyl)pyridine (99 mg, 0.437 mmol), 7-(5-cyclopropylpyrazin-2-yloxy)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one [3:1 (7R,8aS: 7R,8aR) diastereomer ratio](100 mg, 0.365 mmol) from Example 163 Step 3, palladium(II) acetate (4.09 mg, 0.018 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XANTPHOS, 21.09 mg, 0.036 mmol), and cesium carbonate (178 mg, 0.547 mmol). The mixture was purged with nitrogen, and anhydrous dioxane (0.5 mL) was added. The reaction mixture was purged with nitrogen again and was subsequently heated at 110° C. for 16 hours. The mixture was directly loaded and separated by flash chromatography [12 g cartridge, a gradient 0-5% methanol/dichloromethane over 20 minutes] to give crude oily product. The crude product was further purified on 12 g cartridge eluted with a gradient of 0-100% ethyl acetate over 20 minutes to give the title compound (27 mg, 0.064 mmol, 17.66% yield) as the first eluting diastereomer as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.31 (d, J=8.5 Hz, 1H), 8.12 (s, 1H), 7.95 (d, J=1.3 Hz, 1H), 7.85 (dd, J=10.4, 5.6 Hz, 1H), 7.47 (d, J=7.5 Hz, 1H), 5.50 (d, J=5.0 Hz, 1H), 4.47 (ddd, J=7.1, 4.5, 1.7 Hz, 1H), 4.12-3.91 (m, 2H), 3.34 (dt, J=9.7, 4.8 Hz, 2H), 3.19-3.05 (m, 2H), 2.64 (dt, J=14.6, 7.3 Hz, 1H), 2.57-2.42 (m, 1H), 2.00 (tt, J=7.8, 5.3 Hz, 1H), 1.02-0.90 (m, 4H); MS (ESI+) m/z 420 (M+H)+.

後処理

  1. customThe mixture was purged with nitrogen, and anhydrous dioxane (0.5 mL)
  2. additionwas added
  3. customThe reaction mixture was purged with nitrogen again
  4. customseparated by flash chromatography [12 g cartridge
  5. customa gradient 0-5% methanol/dichloromethane over 20 minutes] to give crude oily product
  6. customThe crude product was further purified on 12 g cartridge
  7. washeluted with a gradient of 0-100% ethyl acetate over 20 minutes

出典と根拠

ORDレコード
ord-176c41633b3d48df8c892593052ee2ee
出典データセット
uspto-grants-2014_03
特許番号
US08669255B2

反応ノート

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