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

반응식

HRID 246105 반응식
[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]

참가 물질

8

반응물 4

HCID 6342AcetonitrileHCID 81531Diisopropylethylamine2회HCID 42614784Pyrrolidine-3-carbonitrile hydrochloride2회HCID 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

생성물 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]-amide수율 25.3%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
120 °C

실험 절차

[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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7117f49759744f4c81c50cf69b51be38
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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