Ethylenediamine → 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 246248ノート

反応式

HRID 246248 の反応式
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:45])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH2:33][N:34]([CH3:36])[CH3:35])[N:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[C:1]([CH:3]1[CH2:4][N:5]([C:7](=[O:45])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH2:33][N:34]([CH3:36])[CH3:35])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:6]1)#[N:2]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712890492-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

生成物 1

HCID 712887462-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide収率 67.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a 10 mL pear-shaped flask, 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (130 mg, 0.20 mmol) was combined with CH2Cl2 (1 ml) to give a yellow solution. TFA (0.24 ml, 3.2 mmol) was added and the reaction was stirred at room temperature for 2 h. The crude reaction mixture was concentrated in vacuo and redissolved in CH2Cl2. Ethylenediamine (0.33 ml, 5.0 mmol) was added dropwise and the reaction was stirred at room temperature for 20 min. The crude reaction mixture was concentrated in vacuo. The residue was suspended in cold water and filtered, washing with water then dried on high vacuum to give 70 mg (64%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a yellow solid. MS: (M+H)+=520; 1H NMR (DMSO-d6) δ: 9.14 (s, 1H), 8.70 (d, J=7.0 Hz, 1H), 8.36-8.63 (m, 2H), 8.03 (s, 1H), 7.25 (d, J=6.6 Hz, 1H), 4.48-4.82 (m, 5H), 4.16-4.34 (m, 1H), 4.01-4.15 (m, 1H), 3.86 (d, J=5.1 Hz, 1H), 3.33 (br. s., 1H), 2.80 (t, J=6.1 Hz, 2H), 2.20 (s, 6H), 1.40 (t, J=6.4 Hz, 3H).

後処理

  1. customto give a yellow solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. dissolutionredissolved in CH2Cl2
  5. stirringthe reaction was stirred at room temperature for 20 min
  6. customThe crude reaction mixture
  7. concentrationwas concentrated in vacuo
  8. filtrationfiltered
  9. washwashing with water
  10. customthen dried on high vacuum

出典と根拠

ORDレコード
ord-cf8f7e53bb604959918f666996915af6
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…