Acetonitrile → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide

HRID 246105

反応式

HRID 246105 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([N:23]5[CH2:25][CH:24]5[CH3:26])=[O:22])=[CH:19][N:18]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C(#N)C.Cl.[C:39]([CH:41]1[CH2:45][CH2:44][NH:43][CH2:42]1)#[N:40].C(N(CC)C(C)C)(C)C>C1COCC1.C(OCC)(=O)C.O>[C:39]([CH:41]1[CH2:45][CH2:44][N:43]([CH2:25][CH:24]([NH:23][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH:19]=2)=[O:22])[CH3:26])[CH2:42]1)#[N:40]

参加物

8

反応物 4

HCID 6342AcetonitrileHCID 81531Diisopropylethylamine2 回HCID 42614784Pyrrolidine-3-carbonitrile hydrochloride2 回HCID 86677949[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(2-methyl-aziridin-1-yl)-methanone

生成物 1

HCID 712861852-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide収率 25.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
120 °C

実験手順

[2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(2-methyl-aziridin-1-yl)-methanone (70 mg, 0.14 mmol) was dissolved in 1:1 THF: acetonitrile (1.5 ml). 3-Cyanopyrrolidine hydrochloride (28 mg, 0.21 mmol) and N,N-diisopropylethylamine (37 ul, 0.21 mmol) were added and the reaction was heated in a microwave reactor at 120° C. for 2 h. An additional 0.5 eq of 3-cyanopyrrolidine hydrochloride and N,N-diisopropylethylamine were added and the heating was repeated twice more. Water and ethyl acetate were then added to the cooled solution. The aqueous layer was extracted twice more with ethyl acetate and the combined organics were washed with sodium chloride solution and dried over sodium sulfate. After evaporation of solvent the crude residue was purified by silica gel chromatography (ethyl acetate/dichloromethane) to give 21 mg (25%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-(3-cyano-pyrrolidin-1-yl)-1-methyl-ethyl]-amide. (M+H)+=593.

後処理

  1. extractionThe aqueous layer was extracted twice more with ethyl acetate
  2. washthe combined organics were washed with sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. customAfter evaporation of solvent the crude residue
  5. customwas purified by silica gel chromatography (ethyl acetate/dichloromethane)

出典と根拠

ORDレコード
ord-7117f49759744f4c81c50cf69b51be38
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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