Ethanol → N,N-diethyl-1-(3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide

HRID 1969703노트

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HRID 1969703 반응식
[CH2:1]([N:3]([CH2:38][CH3:39])[S:4]([CH2:7][CH:8]1[CH2:12][CH:11]([C:13]([NH:15][NH:16][C:17]2[N:18]=[C:19]3[CH:25]=[CH:24][N:23](S(C4C=CC(C)=CC=4)(=O)=O)[C:20]3=[N:21][CH:22]=2)=O)[CH:10]([CH2:36][CH3:37])[CH2:9]1)(=[O:6])=[O:5])[CH3:2].O=S(Cl)Cl.CCO>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[CH2:1]([N:3]([CH2:38][CH3:39])[S:4]([CH2:7][CH:8]1[CH2:12][CH:11]([C:13]2[N:18]3[C:19]4[CH:25]=[CH:24][NH:23][C:20]=4[N:21]=[CH:22][C:17]3=[N:16][N:15]=2)[CH:10]([CH2:36][CH3:37])[CH2:9]1)(=[O:6])=[O:5])[CH3:2]

참가 물질

6

반응물 3

HCID 702EthanolHCID 24386Thionyl ChlorideHCID 58557160N,N-diethyl-1-(3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentyl)methanesulfonamide

생성물 1

HCID 136359931N,N-diethyl-1-(3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide수율 58.4%

시약·촉매·용매 2

HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매2회

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온도
80 °C

실험 절차

To a mixture of N,N-diethyl-1-(3-ethyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclopentyl)methanesulfonamide (0.730 g, 1.27 mmol) and TEA (0.529 mL, 3.80 mmol) in 1,4-dioxane (12.7 mL) was added SOCl2 (0.185 mL, 2.53 mmol). The reaction mixture was heated at about 80° C. for about 2 h. The reaction mixture was cooled to ambient temperature and partitioned between saturated aqueous NaHCO3 (30 mL) and DCM (30 mL). The aqueous layer was washed with DCM (2×30 mL). The organic layers were combined, concd under reduced pressure, and purified by silica gel (80 g) chromatography eluting with a gradient of 0-60% MeOH in DCM to give a brown solid. The resulting solid was suspended in Na2CO3 (2 M aqueous, 2 mL), EtOH (2 mL) and 1,4-dioxane (2 mL). The reaction mixture was heated at about 60° C. for about 16 h. The reaction mixture was cooled to ambient temperature and purified by RP-HPLC (Table 1, Method d) to afford N,N-diethyl-1-(3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide (0.300 g, 58%) as a tan solid: LC/MS (Table 1, Method b) Rt=1.89 min; MS m/z: 405 (M+H)+. The solid was further purified by using General Procedure AA to give N,N-diethyl-1-((1S,3R,4R)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide (Table 2, Method 27, Rt=11.8 min, or =negative) (0.021 g, 7%) [Example #1.1]; N,N-diethyl-1-((1R,3S,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methane-sulfonamide (Table 2, Method 27, Rt=11.1 min, or =positive) (0.018 g, 6%) [Example #1.2]; N,N-diethyl-1-((1S,3S,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclo-pentyl)methanesulfonamide (Table 2, Method 27, Rt=10.7 min, or =positive) (0.018 g, 6%) [Example #1.3]; N,N-diethyl-1-((1R,3R,4R)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide (Table 2, Method 28, Rt=20.1 min, or =negative) (0.031 g, 11%) [Example #1.4]; N,N-diethyl-1-((1S,3S,4R)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide (Table 2, Method 27, Rt=12.8 min, or =positive) (0.002 g, 1%) [Example #1.5]; and N,N-diethyl-1-((1R,3S,4R)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)methanesulfonamide (Table 2, Method 27, Rt=12.8 min, or =positive) (0.001 g, 1%) [Example #1.6].

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. custompartitioned between saturated aqueous NaHCO3 (30 mL) and DCM (30 mL)
  3. washThe aqueous layer was washed with DCM (2×30 mL)
  4. custompurified by silica gel (80 g) chromatography
  5. washeluting with a gradient of 0-60% MeOH in DCM
  6. customto give a brown solid
  7. temperatureThe reaction mixture was heated at about 60° C. for about 16 h
  8. temperatureThe reaction mixture was cooled to ambient temperature
  9. custompurified by RP-HPLC (Table 1, Method d)

출처 및 근거

ORD 기록
ord-21980300a92a44ac96e37602bc9c3326
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426411B2

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