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

HRID 245971ノート

反応式

HRID 245971 の反応式
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:40])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([N:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[CH:24]=[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[CH2:6][N:5]([C:7](=[O:40])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([N:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[CH:24]=[N:23]4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712888852-(5-chloro-indazol-1-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 712887072-(5-chloroindazol-1-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 59%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 2-(5-chloro-indazol-1-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 (100 mg, 0.17 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 triturated with EtOAc to afford 45 mg (58%) of 2-(5-chloroindazol-1-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 light yellow solid. MS: (M+Na)+=471; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.88 (s, 1H), 8.95 (s, 1H), 8.72 (dd, J=9.1, 4.5 Hz, 1H), 8.36-8.43 (m, 2H), 7.99-8.07 (m, 1H), 7.94 (d, J=1.9 Hz, 1H), 7.41-7.52 (m, 1H), 4.36-4.66 (m, 3H), 4.06-4.18 (m, 1H), 3.94-4.04 (m, 1H), 3.66-3.81 (m, 1H), 1.26 (t, J=6.0 Hz, 3H).

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 triturated with EtOAc

出典と根拠

ORDレコード
ord-167877f06908441182ff7af867e1f36c
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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