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 1619049노트

반응식

HRID 1619049 반응식
[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]

참가 물질

6

반응물 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

생성물 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}benzamide수율 89%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2d380b5e49ae46448be00aefc5d43914
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772282B2

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