Water → (6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-amine

HRID 2179459Notes

Reaction equation

HRID 2179459 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][N:13]2[C:15]([CH2:18][C:19]([F:22])([F:21])[F:20])=[CH:16][N:17]=[C:12]2[C@@H:11]([NH:23]C(=O)OC(C)(C)C)[CH2:10]1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+].O>ClCCl>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][N:13]2[C:15]([CH2:18][C:19]([F:22])([F:20])[F:21])=[CH:16][N:17]=[C:12]2[C@@H:11]([NH2:23])[CH2:10]1

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86698904tert-Butyl [(6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl]carbamate

Product 1

HCID 86698230(6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-amineYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl [(6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl]carbamate (59.0 mg, 0.137 mmol) in dichloromethane (1.37 mL) was added trifluoroacetic acid (105 μL, 1.37 mmol), and the mixture was stirred 1 h. Saturated aqueous sodium bicarbonate was added. Water was added, and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile 30% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (23 mg). MS 332.3 (M+1).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile 30% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-3bc0fe0567d44d59b592844a5a017b7d
Source dataset
uspto-grants-2015_06
Patent number
US09067941B2

Reaction notes

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