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 1969678ノート

反応式

HRID 1969678 の反応式
[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]

参加物

5

反応物 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

生成物 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)cyclopentanol収率 34.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-44e686a2a29448af9af300fb2c86150d
出典データセット
uspto-grants-2013_04
特許番号
US08426411B2

反応ノート

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