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 246363노트

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HRID 246363 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 81.2%

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. overnight then concentrated. The residue was re-dissolved in 5 mL of a mixture of dichloromethane/MeOH/ammonium hydroxide (60:10:1) and stirred at 25° C. for 3 h, then evaporated to a yellow solid, dissolved in dichloromethane (containing a few drops of MeOH) and purified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane). 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%) as a white solid. MS (M+H)+=461; 1H NMR (DMSO-d6) δ: 9.11 (s, 1H), 8.37 (s, 1H), 8.17 (d, J=1.9 Hz, 1H), 7.90 (s, 1H), 7.87 (s, 1H), 7.27-7.38 (m, 2H), 7.06-7.15 (m, 1H), 6.91 (t, J=2.1 Hz, 1H), 6.80-6.89 (m, 1H), 4.20 (s, 3H), 4.11 (dq, J=13.9, 6.8 Hz, 1H), 1.06 (d, J=6.4 Hz, 6H).

후처리

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

출처 및 근거

ORD 기록
ord-f1f1e829c79847fd934f36aee7694cab
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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