Ethylenediamine → 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide

HRID 1898496ノート

反応式

HRID 1898496 の反応式
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:15][C@H:16]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:17](=[O:23])[N:18]4[CH2:22][CH2:21][CH2:20][CH2:19]4)=[O:14])=[CH:11][N:10](COCC[Si](C)(C)C)[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C(N)CN.CCOC(C)=O>ClCCl>[CH3:25][C:24]([CH3:27])([CH3:26])[C@@H:16]([NH:15][C:13]([C:12]1[C:6]2[C:7](=[N:8][CH:9]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[N:5]=2)[NH:10][CH:11]=1)=[O:14])[C:17]([N:18]1[CH2:19][CH2:20][CH2:21][CH2:22]1)=[O:23]

参加物

6

反応物 4

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 67386346(R)-2-cyclopropyl-N-(3,3-dimethyl-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

生成物 1

HCID 533858362-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide収率 50.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a 10 mL round-bottomed flask, (R)-2-cyclopropyl-N-(3,3-dimethyl-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.19 g, 0.34 mmol) was dissolved in dichloromethane (1.4 mL). Trifluoroacetic acid (1.05 mL, 13.7 mmol) was added and the light yellow reaction mixture was stirred at room temperature for 2 h then concentrated under reduced pressure. The residue was dissolved in toluene (3 mL), concentrated and then placed under high vacuum for 30 min. The resultant foam was dissolved in dichloromethane (1.4 mL) and ethylenediamine (1.40 mL, 20.7 mmol) was added. The light yellow reaction mixture was stirred at room temperature for 2 h then quenched with water and extracted with EtOAc (2×50 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 8 g SiO2 with MeOH/CH2Cl2 (gradient: 0-10% MeOH) to afford a yellow solid. Trituration with EtOAc provided 63 mg (50%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2,2-dimethyl-1-(pyrrolidine-1-carbonyl)-propyl]-amide as a white powder. MS: (M+H)+=370; mp=201.0-203.0.

後処理

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in toluene (3 mL)
  3. concentrationconcentrated
  4. waitplaced under high vacuum for 30 min
  5. dissolutionThe resultant foam was dissolved in dichloromethane (1.4 mL)
  6. stirringThe light yellow reaction mixture was stirred at room temperature for 2 h
  7. customthen quenched with water
  8. extractionextracted with EtOAc (2×50 mL)
  9. washThe combined organic layers were washed with water and brine
  10. dry with materialthen dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by chromatography over 8 g SiO2 with MeOH/CH2Cl2 (gradient: 0-10% MeOH)
  14. customto afford a yellow solid

出典と根拠

ORDレコード
ord-8ea215f92a9745e48a3a905659fb60ae
出典データセット
uspto-grants-2013_08
特許番号
US08518945B2

反応ノート

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