rac-tert-butyl N-((1R,3S)-3-aminocyclohexyl)carbamate → tert-butyl N-[(1R,3S)-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]carbamate

HRID 526951Notes

Reaction equation

HRID 526951 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:3]1.[Cl:16][C:17]1[CH:18]=[C:19]2[C:25]([C:26]3[N:31]=[C:30](S(C)=O)[C:29]([F:35])=[CH:28][N:27]=3)=[CH:24][N:23]([S:36]([C:39]3[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=3)(=[O:38])=[O:37])[C:20]2=[N:21][CH:22]=1>C1COCC1>[Cl:16][C:17]1[CH:18]=[C:19]2[C:25]([C:26]3[N:31]=[C:30]([NH:1][C@H:2]4[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH2:3]4)[C:29]([F:35])=[CH:28][N:27]=3)=[CH:24][N:23]([S:36]([C:39]3[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=3)(=[O:38])=[O:37])[C:20]2=[N:21][CH:22]=1

Participants

4

Reactant 2

HCID 59710757rac-tert-butyl N-((1R,3S)-3-aminocyclohexyl)carbamateHCID 672853215-Chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridine

Product 1

HCID 68007892tert-butyl N-[(1R,3S)-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]carbamateYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl N-[(1R,3S)-3-aminocyclohexyl]carbamate, 20a, (0.15 g, 0.70 mmol) and 5-chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridine, 1a, (0.49 g, 1.05 mmol) were dissolved in THF (30 mL) and allowed to stir at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was purified by two rounds of silica gel chromatography—first with (0%-10% MeOH/CH2Cl2) second with (10%-50% EtOAc/hexanes) to provide tert-butyl N-[(1R,3S)-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]cyclohexyl]carbamate (20b) (330 mg, 38%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was purified by two rounds of silica gel chromatography—first with (0%-10% MeOH/CH2Cl2) second with (10%-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d669e9d464344c2db219be7750e34be4
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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