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

HRID 1969561Notes

Reaction equation

HRID 1969561 reaction equation
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]

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-69434bd8012640bb9f929b5fa40bc485
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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