Ethylenediamine → 2-(5-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide

HRID 245808노트

반응식

HRID 245808 반응식
[CH3:1][C@H:2]([NH:7][C:8]([C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([Cl:28])[CH:26]=4)[N:21]([CH3:29])[N:20]=3)[N:17]=2)[N:12](COCC[Si](C)(C)C)[CH:11]=1)=[O:9])[C:3]([CH3:6])([CH3:5])[CH3:4].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][C@H:2]([NH:7][C:8]([C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([Cl:28])[CH:26]=4)[N:21]([CH3:29])[N:20]=3)[N:17]=2)[NH:12][CH:11]=1)=[O:9])[C:3]([CH3:6])([CH3:5])[CH3:4]

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861652-(5-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide

생성물 1

HCID 712881472-(5-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide수율 85.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

In a round-bottomed flask, 2-(5-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide (90 mg, 0.17 mmol) was dissolved in dichloromethane (0.8 ml) and trifluoroacetic acid (0.5 ml, 6.6 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (0.8 ml) and ethylenediamine (0.7 ml, 9.9 mmol) was added. The solution was stirred at room temperature for 1.5 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, rinsed with hot water and ethyl acetate then dried under high vacuum to provide 60 mg (83%) of 2-(5-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide as a light yellow powder. MS: (M+H)+=411; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.43 (br. s., 1H), 9.08 (s, 1H), 8.45 (s, 1H), 8.33 (s, 1H), 8.00 (d, J=10.2 Hz, 1H), 7.85 (d, J=8.9 Hz, 1H), 7.55 (dd, J=8.9, 1.5 Hz, 1H), 4.20 (s, 3H), 4.06-4.28 (m, 1H), 1.33 (d, J=6.8 Hz, 3H), 0.92 (s, 9H).

후처리

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (0.8 ml)
  3. stirringThe solution was stirred at room temperature for 1.5 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resultant suspension was filtered
  7. washrinsed with hot water and ethyl acetate
  8. customthen dried under high vacuum

출처 및 근거

ORD 기록
ord-fdeadeed73ce4d13b29dbbc4124ce56e
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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