Trifluoroacetic acid → N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246355노트

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HRID 246355 반응식
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[CH2:23][CH2:22][C:21]([CH3:26])([CH3:25])[CH2:20][C:19]=4[N:18]([CH3:27])[N:17]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>ClCCl>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[CH2:23][CH2:22][C:21]([CH3:25])([CH3:26])[CH2:20][C:19]=4[N:18]([CH3:27])[N:17]=3)[N:14]=2)[NH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2]

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 71279665N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

생성물 1

HCID 71279800N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide수율 81.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
25 °C

실험 절차

To a solution of N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (90 mg, 181 μmol) in dichloromethane (3 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol). The reaction mixture was stirred at 25° C. for 18 h then concentrated. The residue was re-dissolved in 5 mL of a solution of dichloromethane/MeOH/ammonium hydroxide (60:10:1) and stirred at 25° C. for 3 h, then evaporated and purified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane, 15 min gradient). The pure product was suspended in dichloromethane and cyclohexane added to promote solid formation. The solid was separated by decanting the mother liquors and then dried to give N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (54 mg, 147 μmol, 81.3%) as a white solid. MS (M+H)+=367; 1H NMR (300 MHz, DMSO-d6) δ ppm 12.68 (m, 1H), 8.91 (s, 1H), 8.31 (s, 1H), 8.04 (d, J=8.31 Hz, 1H), 4.17-4.26 (m, 1H), 3.75 (s, 3H), 2.92 (t, J=6.42 Hz, 2H), 1.52 (t, J=6.42 Hz, 2H), 1.37 (s, 2H), 1.22 (d, J=6.42 Hz, 6H), 1.01 (s, 6H).

후처리

  1. concentrationthen concentrated
  2. dissolutionThe residue was re-dissolved in 5 mL of a solution of dichloromethane/MeOH/ammonium hydroxide (60:10:1)
  3. stirringstirred at 25° C. for 3 h
  4. customevaporated
  5. custompurified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane, 15 min gradient)
  6. additioncyclohexane added
  7. customThe solid was separated
  8. customby decanting the mother liquors
  9. customdried

출처 및 근거

ORD 기록
ord-fbbd836633bc4b78ace82d6c4364282d
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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