Ethylenediamine → 2-(5,6-dichloro-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 245968

反応式

HRID 245968 の反応式
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:45])[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:36])=[C:32]([Cl:35])[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].C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:45])[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:36])=[C:32]([Cl:35])[CH:33]=5)[CH:28]=[N:27]4)[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:11]2[CH2:12][CH2:13]2)[CH2:5][CH2:4]1)#[N:2]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712889262-(5,6-dichloro-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 712885342-(5,6-dichloro-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%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-(5,6-dichloro-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 (220 mg, 0.33 mmol) in CH2Cl2 (4 mL) was added TFA (2.0 mL, 26.0 mmol). The yellow reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (4 mL) and ethylenediamine (0.4 mL, 5.92 mmol) was added. The reaction mixture was stirred at room temperature for 0.5 h then quenched with water and extracted with CH2Cl2 (3×). The combined organics were concentrated and the residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH) then triturated with Et2O to afford 95 mg (54%) of 2-(5,6-dichloro-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 light yellow solid. MS: (M+Na)+=559; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.91 (br. s., 1H), 8.91 (s, 1H), 8.79 (s, 1H), 8.44 (s, 1H), 8.41 (d, J=7.9 Hz, 1H), 8.29 (d, J=7.9 Hz, 1H), 8.18 (s, 1H), 4.77 (t, J=7.6 Hz, 1H), 3.59-3.86 (m, 2H), 3.32-3.46 (m, 1H), 2.95-3.05 (m, 2H), 1.45-1.92 (m, 4H), 1.24 (br. s., 1H), 0.32-0.48 (m, 4H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (4 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 0.5 h
  4. customthen quenched with water
  5. extractionextracted with CH2Cl2 (3×)
  6. concentrationThe combined organics were concentrated
  7. customthe residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH)
  8. customthen triturated with Et2O

出典と根拠

ORDレコード
ord-4178f25755f24ed1a70bb25a0a2d3b86
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

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