Ethylenediamine → 2-(5-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

HRID 245802노트

반응식

HRID 245802 반응식
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([C:28]4[C:36]5[C:31](=[CH:32][CH:33]=[C:34]([Cl:37])[CH:35]=5)[N:30]([CH3:38])[N:29]=4)[N:26]=3)[N:21](COCC[Si](C)(C)C)[CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([C@H:11]([NH:16][C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([C:28]4[C:36]5[C:31](=[CH:32][CH:33]=[C:34]([Cl:37])[CH:35]=5)[N:30]([CH3:38])[N:29]=4)[N:26]=3)[NH:21][CH:20]=2)=[O:18])[C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712888282-(5-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide

생성물 1

HCID 712862132-(5-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide수율 25.3%

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 [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide (0.158 g, 0.193 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.6 ml, 7.8 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was redissolved in dichloromethane (1 ml) and ethylenediamine (0.8 ml, 11.7 mmol) was added. The solution was stirred at room temperature for 1 h then quenched with water and extracted with EtOAc (2×). 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 silica gel with EtOAc/hexanes (gradient 0-100% EtOAc) to afford 26 mg (24%) of 2-(5-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyano-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-amide as an off-white solid. MS: (M+H)+=533; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.92 (br. s., 1H), 9.09 (s, 1H), 8.73 (d, J=6.8 Hz, 1H), 8.61 (t, J=8.1 Hz, 1H), 8.46 (d, J=9.1 Hz, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.50 (d, J=9.1 Hz, 1H), 5.20 (d, J=9.4 Hz, 1H), 4.19 (s, 3H), 3.97-4.12 (m, 1H), 3.35-3.91 (m, 2H), 3.01-3.23 (m, 2H), 1.39-2.07 (m, 4H), 1.04 (d, J=6.4 Hz, 9H).

후처리

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (1 ml)
  3. stirringThe solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc)

출처 및 근거

ORD 기록
ord-9c66cf2075984b7483b5a1ca6dc0a48e
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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