Lithium Hydroxide → (S)-(1S,3R)-3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-pyrimidin-4-yl)amino)cyclohexyl 3-fluoropyrrolidine-1-carboxylate

HRID 75054Notes

Reaction equation

HRID 75054 reaction equation
[F:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C@H:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17]3[C:22]([F:23])=[CH:21][N:20]=[C:19]([C:24]4[C:32]5[C:27](=[N:28][CH:29]=[C:30]([F:33])[CH:31]=5)[N:26](S(C5C=CC(C)=CC=5)(=O)=O)[CH:25]=4)[N:18]=3)[CH2:11]2)=[O:8])[CH2:3]1.[Li+].[OH-].[Cl-].[NH4+]>C1COCC1>[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C@H:10]2[CH2:15][CH2:14][CH2:13][C@@H:12]([NH:16][C:17]3[C:22]([F:23])=[CH:21][N:20]=[C:19]([C:24]4[C:32]5[C:27](=[N:28][CH:29]=[C:30]([F:33])[CH:31]=5)[NH:26][CH:25]=4)[N:18]=3)[CH2:11]2)=[O:8])[CH2:3]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 25517Ammonium ChlorideHCID 68007584(R)-(1S,3R)-3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)cyclohexyl 3-fluoropyrrolidine-1-carboxylate

Product 1

HCID 68008532(S)-(1S,3R)-3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-pyrimidin-4-yl)amino)cyclohexyl 3-fluoropyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of crude (R)-(1S,3R)-3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)cyclohexyl 3-fluoropyrrolidine-1-carboxylate, 75d, (0.119 g, 0.019 mmol) in THF (2 mL) was added 5 mL 2N LiOH (10 mmol). The reaction mixture was heated at 50° C. for 2 hours. The mixture was diluted into aqueous saturated ammonium chloride (2 mL), and extracted with EtOAc (2×10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified on the semi-prep HPLC, 10-70% CH3CN/H2O; Three runs; homogeneous fractions were combined and the solvent removed under a stream of nitrogen and then removed residual solvent on roto-evaporator to afford 74 mg of the desired product: LCMS RT=2.15 min (M+H) 461.51.

Workup

  1. extractionextracted with EtOAc (2×10 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified on the semi-prep HPLC, 10-70% CH3CN/H2O
  6. customthe solvent removed under a stream of nitrogen
  7. customremoved residual solvent
  8. customon roto-evaporator

Sources & evidence

ORD record
ord-ff12865d896b48e0b13366bfecdc7c01
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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