Potassium Carbonate → (S)-tert-butyl 3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)piperidine-1-carboxylate

HRID 74871Notes

Reaction equation

HRID 74871 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.Cl[C:31]1[N:36]=[C:35]([NH:37][C@H:38]2[CH2:43][CH2:42][CH2:41][N:40]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:39]2)[C:34]([F:51])=[CH:33][N:32]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:31]3[N:36]=[C:35]([NH:37][C@H:38]4[CH2:43][CH2:42][CH2:41][N:40]([C:44]([O:46][C:47]([CH3:49])([CH3:48])[CH3:50])=[O:45])[CH2:39]4)[C:34]([F:51])=[CH:33][N:32]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 75412621tert-butyl (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]piperidine-1-carboxylate2×

Product 1

HCID 68007804(S)-tert-butyl 3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (1.8 g, 4.2 mmol) and tert-butyl (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]piperidine-1-carboxylate, 5a, (1.2 g, 3.7 mmol) in DME (15 mL) and H2O (5 mL) was added K2CO3 (1.7 g, 12.1 mmol). The mixture was purged with nitrogen for 15 min. To the mixture was added tetrakis triphenylphosphine palladium(0) (0.2 g, 0.2 mmol) and the reaction mixture was heated at 90° C. for 3 days. The reaction was cooled down to room temperature and then diluted with EtOAc/H2O. The layers were separated and the organic phase was washed with brine, dried (MgSO4), filtered and evaporated to dryness. The resulting residue was dissolved in CH2Cl2 and purified by silica gel chromatography (0-100% EtOAc/Hexanes) to afford the desired product, 1b.

Workup

  1. customThe mixture was purged with nitrogen for 15 min
  2. temperatureThe reaction was cooled down to room temperature
  3. customThe layers were separated
  4. washthe organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. dissolutionThe resulting residue was dissolved in CH2Cl2
  9. custompurified by silica gel chromatography (0-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-bdd2765f76db4fbba8bb3ac07137d097
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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