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 1969678Notes

Reaction equation

HRID 1969678 reaction equation
[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]

Participants

5

Reactant 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

Product 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)cyclopentanolYield 34.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-44e686a2a29448af9af300fb2c86150d
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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