Hydrochloric Acid → HCID 86677949、化合物

HRID 246104

反応式

HRID 246104 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29](O)=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C([N:35]([CH2:39][CH3:40])[CH:36](C)C)(C)C.CN(C)CCCN=C=NCC.CC1CN1.Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29]([N:35]5[CH2:36][CH:39]5[CH3:40])=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 63772-MethylaziridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 86677949HCID 86677949、化合物収率 64.6%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (100 mg, 0.218 mmol) was suspended in dichloromethane (2.2 ml). 4-Dimethylaminopyridine (5.3 mg, 0.044 mmol), N,N-diisopropylethylamine (76 ul, 0.44 mmol) and then 1-(3-(dimethylamino)-propyl)-3-ethylcarbodiimide (84 mg, 0.44 mmol) were added. The solution was stirred for 5 min then cooled in an ice bath. 2-Methylaziridine (23 ul, 0.33 mmol) was added and the reaction was warmed to room temperature. Stirring was continued until judged to be complete by TLC then water, dilute HCl and ethyl acetate were added. The aqueous layer was extracted once more with ethyl acetate and the combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 70 mg (64%) of [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. 1H NMR (300 MHz, CDCl3) δ ppm 9.23 (s, 1H) 8.76 (d, J=8.7 Hz, 1H) 8.33 (s, 1H) 7.44 (s, 1H) 7.24 (d, J=8.7 Hz, 1H) 5.73 (s, 2H) 4.14 (s, 3H) 3.56-3.65 (m, 6H) 2.80-2.91 (m, 1H) 2.59 (d, J=6.0 Hz, 1H) 2.33 (d, J=3.8 Hz, 1H) 1.41 (d, J=5.3 Hz, 3H) 0.89-0.99 (m, 2H)-0.05 (s, 9H).

後処理

  1. temperaturethen cooled in an ice bath
  2. stirringStirring
  3. extractionThe aqueous layer was extracted once more with ethyl acetate
  4. washthe combined organic layers were washed with sodium bicarbonate solution
  5. dry with materialdried over sodium sulfate
  6. customAfter evaporation the residue
  7. customwas purified by silica gel chromatography (ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-fca5b22889e7498f9094416f8bddae61
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

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