Ethylenediamine → 2-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 245958ノート

反応式

HRID 245958 の反応式
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:44])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([N:26]4[C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[CH:28]=[N:27]4)[N:24]=3)[N:19](COCC[Si](C)(C)C)[CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH:3]1[CH2:4][CH2:5][N:6]([C:9](=[O:44])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([N:26]4[C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[CH:28]=[N:27]4)[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:7][CH2:8]1)#[N:2]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712888882-(5-chloro-indazol-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

生成物 1

HCID 712887612-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide収率 54.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a round-bottomed flask, 2-(5-chloro-indazol-1-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (51 mg, 0.08 mmol) was dissolved in dichloromethane (0.5 ml) and trifluoroacetic acid (0.25 ml, 3.24 mmol) was added. The yellow reaction mixture was stirred at room temperature for 2.5 h then concentrated. The residue was dissolved in dichloromethane (0.5 ml) and ethylenediamine (0.33 ml, 4.89 mmol) was added. The reaction was stirred at room temperature for 1.5 h then quenched with water and extracted with EtOAc (2×30 ml). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc) followed by trituration with EtOAc/hexanes (1:1) to provide 22 mg (52%) of 2-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a yellow solid. MS: (M+H)+=503; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 13.01 (br. s., 1H), 9.10 (s, 1H), 8.94 (dd, J=8.9, 5.1 Hz, 1H), 8.54 (d, J=0.8 Hz, 1H), 8.51 (d, J=6.8 Hz, 1H), 8.29 (d, J=8.3 Hz, 1H), 8.07 (d, J=1.9 Hz, 1H), 7.56 (t, J=6.6 Hz, 1H), 4.92-5.02 (m, 1H), 3.70-4.06 (m, 2H), 3.09-3.68 (m, 3H), 1.50-2.08 (m, 4H), 1.20-1.39 (m, 1H), 0.31-0.61 (m, 4H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.5 ml)
  3. stirringThe reaction was stirred at room temperature for 1.5 h
  4. customthen quenched with water
  5. extractionextracted with EtOAc (2×30 ml)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc)

出典と根拠

ORDレコード
ord-55d3d42290d447cd8981e6037de9d1eb
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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