Hydrochloric Acid → 3,3,3-trifluoro-1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)propan-1-amine hydrochloride

HRID 1969561노트

반응식

HRID 1969561 반응식
C1(C(C2C=CC=CC=2)=[N:8][CH2:9][C:10]2[N:11]=[C:12]3[CH:18]=[CH:17][N:16]([S:19]([C:22]4[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=4)(=[O:21])=[O:20])[C:13]3=[N:14][CH:15]=2)C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:45][C:46]([F:50])([F:49])[CH2:47]I.C([O-])(O)=O.[Na+].[ClH:56]>C1COCC1.C(OC(C)C)(=O)C.CCOC(C)=O>[ClH:56].[F:45][C:46]([F:50])([F:49])[CH2:47][CH:9]([C:10]1[N:11]=[C:12]2[CH:18]=[CH:17][N:16]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:20])=[O:21])[C:13]2=[N:14][CH:15]=1)[NH2:8]

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 516892Sodium BicarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 58557423N-(diphenylmethylene)-1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine

생성물 1

HCID 672169073,3,3-trifluoro-1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)propan-1-amine hydrochloride수율 23%

시약·촉매·용매 3

HCID 7915Isopropyl Acetate용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of N-(diphenylmethylene)-1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine (0.722 g, 1.55 mmol) in THF (3 mL) at about −78° C. was added NaHMDS (0.5 M in THF, 1.55 mL, 1.55 mmol). After about 30 min, 1,1,1-trifluoro-2-iodoethane (1.51 mL, 15.5 mmol) was added to the reaction mixture. After about 4 h, the reaction mixture was allowed to warm to rt slowly over night. After about 15 h, EtOAc (30 mL) and saturated aqueous NaHCO3 (30 mL) were added. The organic layer was separated, concd in vacuo and purified by chromatography on silica gel eluting with EtOAc/heptane (20-50%) to provide the crude alkylated imine. The imine was dissolved in isopropyl acetate (30 mL) and concd HCl (0.50 mL) was added. The reaction mixture was spun on a rotory evaporator for 1 h prior to partial concentration to approx 10 mL. Additional isopropyl acetate (30 mL) was added and the solvent was partially removed in vacuo until approx. 10 mL remained. Et2O (30 mL) was added and the solution was allowed to age for about 30 min. The resulting solids were collected by filtration and dried in vacuo to provide 3,3,3-trifluoro-1-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)propan-1-amine hydrochloride (0.150 g, 23%) as a colorless solid. LC/MS (Table 1, Method a) Rt=1.88 min; MS m/z 385 (M+H)+.

후처리

  1. waitAfter about 4 h
  2. waitAfter about 15 h
  3. customThe organic layer was separated
  4. customconcd in vacuo and purified by chromatography on silica gel eluting with EtOAc/heptane (20-50%)
  5. customto provide the crude alkylated imine
  6. customThe reaction mixture was spun on a rotory evaporator for 1 h
  7. concentrationto partial concentration to approx 10 mL
  8. additionAdditional isopropyl acetate (30 mL) was added
  9. customthe solvent was partially removed in vacuo until approx. 10 mL
  10. additionEt2O (30 mL) was added
  11. waitthe solution was allowed to age for about 30 min
  12. filtrationThe resulting solids were collected by filtration
  13. customdried in vacuo

출처 및 근거

ORD 기록
ord-69434bd8012640bb9f929b5fa40bc485
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426411B2

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