7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine → 7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyltetrahydro-3aH-cyclopenta [d][1,3]dioxol-4-yl)-1H-imidazo [4,5-c]pyridin-4-amine

HRID 470184Notes

Reaction equation

HRID 470184 reaction equation
[F:1][C:2]1[C:3]2[N:11]([C@H:12]3[C@H:19]4[C@H:15]([O:16][C:17]([CH3:21])([CH3:20])[O:18]4)[CH:14]=[C:13]3[F:22])[CH:10]=[N:9][C:4]=2[C:5]([NH2:8])=[N:6][CH:7]=1>CO.[Pd]>[F:1][C:2]1[C:3]2[N:11]([C@H:12]3[C@H:19]4[C@H:15]([O:16][C:17]([CH3:20])([CH3:21])[O:18]4)[CH2:14][CH:13]3[F:22])[CH:10]=[N:9][C:4]=2[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

4

Reactant 1

HCID 583293077-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine

Product 1

HCID 583293087-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyltetrahydro-3aH-cyclopenta [d][1,3]dioxol-4-yl)-1H-imidazo [4,5-c]pyridin-4-amine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta [d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine (5-9) (70 mg, 0.23 mmol, 1 equiv) was dissolved in MeOH (5 mL), the system was placed under nitrogen and 10% Pd/C (25 mg, 0.23 mmol, 1 equiv) was carefully added. The resulting mixture was stirred under a H2 atmosphere (1 atm) until disappearance of the starting material. Hydrogen was removed followed by filtration through a celite plug and washing of the solids with MeOH (4×20 mL). The filtrate was concentrated and the residue was purified via reverse phase chromatography (0-50% CH3CN in water with 0.1% TFA modifier) to afford 7-fluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridin-4-amine (5-12) as a white solid. 1H NMR (500 MHz, CDCl3): δ 7.78 (d, J=3.5 Hz, 1H); 7.73 (s, 1H); 5.20-5.38 (m, 1H); 5.07 (s, 1H); 4.92 (m, 1H); 4.82 (s, 1H); 2.72-2.78 (m, 1H); 2.26-2.37 (m, 1H); 1.61 (s, 3H); 1.32 (s, 3H). LRMS m/z (M+H) 311.0 found, 311.1 required.

Workup

  1. customHydrogen was removed
  2. filtrationfollowed by filtration through a celite plug
  3. washwashing of the solids with MeOH (4×20 mL)
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified via reverse phase chromatography (0-50% CH3CN in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-d72d541a435d4f8992ac70a0bb99190a
Source dataset
uspto-grants-2014_01
Patent number
US08629275B2

Reaction notes

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