4-Methanesulfonylmorpholine → 3-ethyl-1-(morpholinosulfonylmethyl)-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol

HRID 1969678노트

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HRID 1969678 반응식
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)(=[O:4])=[O:3].[Li]CCCC.[CH2:16]([CH:18]1[CH:22]([C:23]2[N:27]3[C:28]4[CH:34]=[CH:33][N:32]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:29]=4[N:30]=[CH:31][C:26]3=[N:25][N:24]=2)[CH2:21][C:20](=[O:43])[CH2:19]1)[CH3:17]>C1COCC1>[CH2:16]([CH:18]1[CH:22]([C:23]2[N:27]3[C:28]4[CH:34]=[CH:33][N:32]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:40])([CH3:42])[CH3:41])[C:29]=4[N:30]=[CH:31][C:26]3=[N:25][N:24]=2)[CH2:21][C:20]([CH2:1][S:2]([N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)(=[O:4])=[O:3])([OH:43])[CH2:19]1)[CH3:17]

참가 물질

5

반응물 3

HCID 5193444-MethanesulfonylmorpholineHCID 585572963-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanoneHCID 178418339Butyllithium

생성물 1

HCID 585572243-ethyl-1-(morpholinosulfonylmethyl)-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol수율 34.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a solution of 4-(methylsulfonyl)morpholine (0.217 g, 1.314 mmol, Preparation #41) in THF (4 mL) at about 0° C. was added n-BuLi (2.5 M in hexanes, 0.53 mL, 1.3 mmol). The reaction mixture was stirred at about 0° C. for about 1 h. The resulting solution was added dropwise to a solution of 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanone (0.350 g, 0.876 mmol, Example #35 Step G) in THF (4 mL) at about 0° C. The reaction mixture was maintained at about 4° C. in a refrigerator for about 48 h. The reaction mixture was partitioned between water (5 mL) and DCM (5 mL) The layers were separated and the aqueous solution was extracted with DCM (2×5 mL). The combined organic extracts were concd under reduced pressure. The product was purified by silica gel chromatography eluting with a gradient of 0-2% MeOH/DCM, then by RP-HPLC (Table 1, Method 1) to give 3-ethyl-1-(morpholinosulfonylmethyl)-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (0.17 g, 34%) as a yellow oil: LC/MS (Table 1, Method b) Rt=2.32 & 2.42 min; MS m/z: 565 (M+H)+.

후처리

  1. temperatureThe reaction mixture was maintained at about 4° C. in a refrigerator for about 48 h
  2. customThe reaction mixture was partitioned between water (5 mL) and DCM (5 mL) The layers
  3. customwere separated
  4. extractionthe aqueous solution was extracted with DCM (2×5 mL)
  5. customThe product was purified by silica gel chromatography
  6. washeluting with a gradient of 0-2% MeOH/DCM

출처 및 근거

ORD 기록
ord-44e686a2a29448af9af300fb2c86150d
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426411B2

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