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Diisopropylethylamine → 2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)-N-(tetrahydro-pyran-3-yl)-amide

HRID 246133
ノート
印刷プレビュー

反応式

HRID 246133 の反応式
FC(F)(F)C(O)=O.[O:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH2:14])[CH2:9]1.[Cl:15][C:16]1[CH:24]=[C:23]2[C:19]([C:20]([C:26]3[N:27]=[C:28]4[C:34]([C:35](O)=[O:36])=[CH:33][N:32]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[C:29]4=[N:30][CH:31]=3)=[N:21][N:22]2[CH3:25])=[CH:18][CH:17]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(#N)C.C(OCC)(=O)C.O>[O:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C:35]([C:34]2[C:28]3[C:29](=[N:30][CH:31]=[C:26]([C:20]4[C:19]5[C:23](=[CH:24][C:16]([Cl:15])=[CH:17][CH:18]=5)[N:22]([CH3:25])[N:21]=4)[N:27]=3)[N:32]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[CH:33]=2)=[O:36])[CH2:9]1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2 回HCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 71280724(S)-(Tetrahydro-pyran-3-yl)amine trifluoroacetate

生成物 1

HCID 71286038
2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)-N-(tetrahydro-pyran-3-yl)-amide
収率 58%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(S)-(Tetrahydro-pyran-3-yl)amine trifluoroacetate (crude from Step 4) was dissolved in acetonitrile (1.8 ml) to which was then added 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (80 mg, 0.175 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (84 mg, 0.26 mmol) and N,N-diisopropylethylamine (0.15 ml, 0.87 mmol). The reaction was stirred at room temperature for 18 h. Additional O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (50 mg, 0.16 mmol) and N,N-diisopropylethylamine (0.11 ml, 0.63 mmol) were added and stirring was continued for 24 h. Water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford 55 mg (58%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (S)—N-(tetrahydro-pyran-3-yl)-amide. (M+Na)+=563.

後処理

  1. stirringstirring
  2. waitwas continued for 24 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. customAfter evaporation
  8. customthe residue was purified by silica gel chromatography (ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-68eb81cff066444d86d0465b0438b059
出典データセット
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08658646B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート