Diisopropylethylamine → N-{(4aR,7aR)-7a-(5-Cyanothiophen-2-yl)-6-[5-fluoro-4-(2-hydroxypropan-2-yl)pyrimidin-2-yl]-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl}benzamide

HRID 338147ノート

反応式

HRID 338147 の反応式
[C:1]([C:3]1[S:7][C:6]([C@:8]23[CH2:16][NH:15][CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:9]3)=[CH:5][CH:4]=1)#[N:2].C(N(C(C)C)CC)(C)C.Cl[C:36]1[N:41]=[C:40]([C:42]([OH:45])([CH3:44])[CH3:43])[C:39]([F:46])=[CH:38][N:37]=1>O1CCOCC1.C(OCC)(=O)C>[C:1]([C:3]1[S:7][C:6]([C@:8]23[CH2:16][N:15]([C:36]4[N:41]=[C:40]([C:42]([OH:45])([CH3:44])[CH3:43])[C:39]([F:46])=[CH:38][N:37]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:17][C:18](=[O:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:9]3)=[CH:5][CH:4]=1)#[N:2]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 866978842-(2-Chloro-5-fluoropyrimidin-4-yl)propan-2-olHCID 86762239N-[(4aR,7aR)-7a-(5-cyanothiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

生成物 1

HCID 86762238N-{(4aR,7aR)-7a-(5-Cyanothiophen-2-yl)-6-[5-fluoro-4-(2-hydroxypropan-2-yl)pyrimidin-2-yl]-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl}benzamide収率 89%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a stirred clear and colorless solution of N-[(4aR,7aR)-7a-(5-cyanothiophen-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (0.806 mmol) in 1,4-dioxane (16 mL) is added diisopropylethylamine (422 μL, 2.42 mmol) and 2-(2-chloro-5-fluoropyrimidin-4-yl)propan-2-ol (1.54 g, 8.06 mmol). The solution is heated to reflux for 14 hours. The pale yellow solution is allowed to cool, diluted with ethyl acetate (80 mL) and hexanes (20 mL), and washed with dilute aqueous sodium bicarbonate (30 mL, prepared from saturated aqueous sodium bicarbonate (15 mL) and water (15 mL), water (2×20 mL), and brine (20 mL). The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography, eluting with a hexanes/diethyl ether, gradient from 80:20 to 0:100, to give the title compound (374 mg, 89% over two steps) as a pale yellow glass. MS/ES (m/z) 523.2 (M+H).

後処理

  1. temperatureThe solution is heated
  2. temperatureto reflux for 14 hours
  3. temperatureto cool
  4. washwashed with dilute aqueous sodium bicarbonate (30 mL
  5. customprepared from saturated aqueous sodium bicarbonate (15 mL) and water (15 mL), water (2×20 mL), and brine (20 mL)
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by silica gel chromatography
  10. washeluting with a hexanes/diethyl ether, gradient from 80:20 to 0:100

出典と根拠

ORDレコード
ord-558edb731b4c4a13ac3804bcba552c4b
出典データセット
uspto-grants-2014_11
特許番号
US08889856B2

反応ノート

読み込み中…