tert-butyl (3R)-3-aminopiperidine-1-carboxylate → (R)-tert-butyl 3-((1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino)piperidine-1-carboxylate

HRID 588360Notes

Reaction equation

HRID 588360 reaction equation
CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.CC([O-])(C)C.[Na+].Cl[C:46]1[N:47]=[CH:48][CH:49]=[C:50]2[CH:54]=[CH:53][N:52]([CH3:55])[C:51]=12.[NH2:56][C@@H:57]1[CH2:62][CH2:61][CH2:60][N:59]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:58]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:55][N:52]1[C:51]2=[C:46]([NH:56][C@@H:57]3[CH2:62][CH2:61][CH2:60][N:59]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:58]3)[N:47]=[CH:48][CH:49]=[C:50]2[CH:54]=[CH:53]1

Participants

8

Reactant 4

HCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 25112535BrettphosHCID 594244767-chloro-1-methyl-1H-pyrrolo[2,3-c]pyridine2×

Product 1

HCID 117652959(R)-tert-butyl 3-((1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino)piperidine-1-carboxylateYield 94%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

A solution of Pd2(dba)3 (1.53 g, 1.68 mmol), BrettPhos (1.86 g, 3.36 mmol) in toluene (40 mL) under N2 atmosphere was stirred for 20 min. NaOtBu (3.23 g, 33.6 mmol), the compound from Step 1 7-chloro-1-methyl-1H-pyrrolo[2,3-c]pyridine (2.80 g, 16.8 mmmol) and tert-butyl (3R)-3-aminopiperidine-1-carboxylate (4.04 g, 20.2 mmol) were added. The reaction was stirred at 105° C. for 3 h. The reaction mixture was poured into water (20 mL) and extracted with EtOAc (3×20 mL). The organic layers were dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography, eluting with a gradient of 17-50% EtOAc/petroleum ether to give the title compound as a brown solid (5.2 g, 94%).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with a gradient of 17-50% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-c656875441234c8a95f0cc918694e41d
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

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