Selectfluor → tert-Butyl (1S,2R)-2-(4-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 2092822Notes

Reaction equation

HRID 2092822 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[C:13]3[C:14](=[O:17])[NH:15][CH2:16][C:12]=3[CH:11]=[C:10]([NH:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]3[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[N:9]=2)[CH:5]=[N:4]1)[CH3:2].[B-](F)(F)(F)[F:34].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(Cl)Cl>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[C:13]3[C:14](=[O:17])[NH:15][CH2:16][C:12]=3[C:11]([F:34])=[C:10]([NH:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]3[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[N:9]=2)[CH:5]=[N:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 2724933Selectfluor2×HCID 86654724tert-Butyl (1S,2R)-2-(4-(1-ethyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 1

HCID 89553006tert-Butyl (1S,2R)-2-(4-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-Butyl (1S,2R)-2-(4-(1-ethyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (69.7 mg, 0.158 mmol) in DCM (5 mL) was cooled to 0° C. SELECTFLUOR® (84 mg, 0.237 mmol) was added. The mixture was left stirring in an ice bath and was allowed to warm slowly to RT with stirring overnight. Additional SELECTFLUOR® (2 eq) was added and the reaction was stopped after 2 h. After removal of solvent, the residue was diluted with EtOAc (10 mL) and washed with saturated aq NaHCO3 (5 mL), water (5 mL), and brine (5 mL). The organic layers were combined, dried over Na2SO4, and concentrated to a brown residue. The resulting crude material was reconstituted in MeOH/DCM (6 mL) and was purified via preparative HPLC. The fractions were collected and ACN was removed via rotary evaporation. The resulting aq solution was neutralized with saturated aq NaHCO3, washed with EtOAc (2×200 mL), dried over Na2SO4, and filtered. The organic phase was stripped to dryness via rotary evaporation to yield the title compound (20 mg, 28%). [M+H] calc'd for C23H31FN6O3, 459. found, 459.

Workup

  1. waitThe mixture was left
  2. stirringwith stirring overnight
  3. customAfter removal of solvent
  4. additionthe residue was diluted with EtOAc (10 mL)
  5. washwashed with saturated aq NaHCO3 (5 mL), water (5 mL), and brine (5 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to a brown residue
  8. customwas purified via preparative HPLC
  9. customThe fractions were collected
  10. customACN was removed via rotary evaporation
  11. washwashed with EtOAc (2×200 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. customThe organic phase was stripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-54ed13bca8674b77981591fe3b0177ac
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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