Methanol → N-(3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentyl)cyclopropanesulfonamide

HRID 1969837ノート

反応式

HRID 1969837 の反応式
[CH3:1][CH:2]1[CH:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]=4[N:14]=[CH:15][C:10]3=[N:9][CH:8]=2)[CH2:5][CH:4]([NH2:27])[CH2:3]1.CCN(C(C)C)C(C)C.[CH:37]1([S:40](Cl)(=[O:42])=[O:41])[CH2:39][CH2:38]1.CO>C(Cl)Cl>[CH3:1][CH:2]1[CH:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]=4[N:14]=[CH:15][C:10]3=[N:9][CH:8]=2)[CH2:5][CH:4]([NH:27][S:40]([CH:37]2[CH2:39][CH2:38]2)(=[O:42])=[O:41])[CH2:3]1

参加物

6

反応物 4

HCID 887MethanolHCID 81531Diisopropylethylamine2 回HCID 2760919Cyclopropanesulfonyl chloride2 回HCID 585575733-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine

生成物 1

HCID 58557168N-(3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentyl)cyclopropanesulfonamide収率 52.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine (0.27 g, 0.7 mmol) and DIEA (0.18 mL, 1.05 mmol) in DCM (5 mL) was added cyclopropanesulfonyl chloride (0.098 g, 0.7 mmol) drop-wise. The resulting mixture was stirred at ambient temperature for about 1 h. Another 0.18 mL of DIEA and 0.098 g of cyclopropanesulfonyl chloride were added and the reaction was continued for about 3 h. The solvent was removed and the residue was partitioned between saturated aqueous ammonium chloride and EtOAc (20 mL each). The organic layer was washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concd. The residue was purified by silica gel chromatography (100% DCM for 5 min, then to 6% MeOH in DCM over next 30 min) to yield N-(3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentyl)cyclopropanesulfonamide (0.18 g, 52% yield) as an off-white solid. LC/MS (Table 1, Method a) Rt=2.45 min; MS m/z 490 (M+H)+.

後処理

  1. waitthe reaction was continued for about 3 h
  2. customThe solvent was removed
  3. customthe residue was partitioned between saturated aqueous ammonium chloride and EtOAc (20 mL each)
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe residue was purified by silica gel chromatography (100% DCM for 5 min

出典と根拠

ORDレコード
ord-0235329ce7b74294909f0feb55755828
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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