Sodium hydride → 2-(2-Chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)phenyl)(6-chloropyridazin-3-yl)methanone

HRID 46205

반응식

HRID 46205 반응식
[H-].[Na+].[Cl:3][C:4]1C=[CH:8][C:7]([CH:10]2[C@H:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@@H:14]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@H:13]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C@@H:12]([CH2:40][O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[O:11]2)=[CH:6][C:5]=1CC#N.ClC1N=[N:55][C:56]([Cl:59])=[CH:57][CH:58]=1.ClC1C=CC([C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)[O:68]2)=CC=1CC1SC(SC)=NN=1.C[N:87]([CH3:91])[C:88](=O)[CH3:89]>>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C@H:10]2[C@H:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@@H:14]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@H:13]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C@@H:12]([CH2:40][O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[O:11]2)=[CH:8][C:91]=1[N:87]1[C:88]([CH:89]=[O:68])=[CH:58][CH:57]=[C:56]([Cl:59])[NH:55]1

참가 물질

6

반응물 5

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 673313,6-DichloropyridazineHCID 46229266(2S,3R,4R,5S,6R)-2-(4-Chloro-3-((5-(methylthio)-1,3,4-thiadiazol-2-yl)methyl)phenyl)-6-(hydroxymethyl)-tetrahydro-2H-pyran-3,4,5-triolHCID 672877902-(2-Chloro-5-((3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)phenyl)acetonitrile2회

생성물 1

HCID 866644292-(2-Chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)phenyl)(6-chloropyridazin-3-yl)methanone

반응 조건

온도
0 °C

실험 절차

Sodium hydride (593 mg; 14.8 mmol; 60% in mineral oil) was added to stirred solution of Intermediate 1 (compound 6, 5.00 g; 7.42 mmol) in 20 mL of N,N-dimethylacetamide (DME) at 0° C. under nitrogen gas. The reaction mixture was stirred for 30 min, and 3,6-dichloropyridazine (compound 22, 1.25 g; 8.16 mmol) was added in one portion. The ice bath was removed, and the reaction mixture was stirred at room temperature for 3.5 h. Cooled to 0° C., H2O2 (2.50 mL) was added to reaction mixture and left stirring additional hour warm-up to room temperature. The reaction solution was washed with 1N HCl solution, 1N NaOH solution and brine. The organic layer was collected, and evaporated under a vacuum. The crude mixture was further purified by flash column chromatography (Biotage SP1™) to obtain 3.10 g (4.00 mmol; 54%) of the title compound as orange oil.

후처리

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at room temperature for 3.5 h
  3. additionH2O2 (2.50 mL) was added to reaction mixture
  4. waitleft
  5. stirringstirring additional hour
  6. temperaturewarm-up to room temperature
  7. washThe reaction solution was washed with 1N HCl solution, 1N NaOH solution and brine
  8. customThe organic layer was collected
  9. customevaporated under a vacuum
  10. customThe crude mixture was further purified by flash column chromatography (Biotage SP1™)

출처 및 근거

ORD 기록
ord-86014667753642a695508f002b398cac
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541380B2

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