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

HRID 246174노트

반응식

HRID 246174 반응식
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:43])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([Cl:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH2:9][O:10][CH3:11])[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O.C(N)CN>ClCCl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:43])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([Cl:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH2:9][O:10][CH3:11])[CH2:4]1)#[N:2]

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712889482-(6-chloro-1-methyl-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-methoxymethyl-2-oxo-ethyl]-amide

생성물 1

HCID 712887042-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-amide수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

In a 25 mL round-bottom flask, 2-(6-chloro-1-methyl-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-methoxymethyl-2-oxo-ethyl]-amide (44 mg, 0.071 mmol) and TFA (1.8 ml, 23.4 mmol) were combined with dichloromethane (6 ml) to give an orange solution. The reaction mixture was stirred at room temperature for 2.5 h then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (4 mL) and ethylenediamine (0.30 ml, 4.4 mmol) was added. The reaction mixture was stirred at room temperature for 18 h then concentrated and the residue was precipitated with water. The suspension was stirred for 1 h and the crude solid collected by filtration. The crude solid was purified by trituration (hot dichloromethane/heptane) to afford 21 mg (59%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-amide as a white solid. MS: [M+H]+=492; 1H NMR (300 MHz, DMSO-d6) δ: 12.72 (br. s, 1H), 9.16 (s, 1H), 8.74 (d, J=8.7 Hz, 1H), 8.55 (d, J=8.3 Hz, 1H), 8.50 (d, J=4.9 Hz, 1H), 7.97 (d, J=1.5 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 4.86-5.04 (m, 1H), 4.46-4.73 (m, 2H), 4.17-4.19 (m, 1H), 4.16-4.28 (m, 4H), 4.04-4.16 (m, 1H), 3.77-3.93 (m, 1H), 3.72 (dd, J=9.5, 4.9 Hz, 1H), 3.59-3.68 (m, 1H), 3.27 (app d, J=4.9 Hz, 3H).

후처리

  1. customto give an orange solution
  2. concentrationthen concentrated under reduced pressure
  3. dissolutionThe resultant crude solid was dissolved in dichloromethane (4 mL)
  4. stirringThe reaction mixture was stirred at room temperature for 18 h
  5. concentrationthen concentrated
  6. customthe residue was precipitated with water
  7. stirringThe suspension was stirred for 1 h
  8. filtrationthe crude solid collected by filtration
  9. customThe crude solid was purified by trituration (hot dichloromethane/heptane)

출처 및 근거

ORD 기록
ord-9607e240f47a48e494938248d162d1d7
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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