tert-butyl (3R)-3-aminopiperidine-1-carboxylate → HCID 86702326, compound

HRID 2279064Notes

Reaction equation

HRID 2279064 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[C:12]([O:17][CH3:18])=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:9][N:10]=2)[N:7]=1.[NH2:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[CH3:18][O:17][C:12]1[C:11]([C:8]2[N:6]3[N:7]=[C:2]([NH:19][C@@H:20]4[CH2:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[CH:16][CH:15]=[CH:14][N:13]=1

Participants

6

Reactant 4

HCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 86702325HCID 86702325, compound

Product 1

HCID 86702326HCID 86702326, compoundYield 42.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-chloro-3-(2-methoxypyridin-3-yl)imidazo[1,2-b]pyridazine (Preparation 2, 0.15 g, 0.58 mmol), tert-butyl (3R)-3-aminopiperidine-1-carboxylate (0.23 g, 1.15 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (0.03 g, 0.09 mmol), sodium tert-butoxide (0.08 g, 0.81 mmol) and toluene (4 mL) in a Schlenk vial was subjected to three cycles of evacuation backfilling with argon. Tris(dibenzylidene acetone)dipalladium(0) (0.04 g, 0.04 mmol) was then added and the resulting mixture was subjected to three further cycles of evacuation backfilling before being heated at 110° C. for 20 hours. Subsequently, the reaction was cooled down, filtered through Celite® eluting with ethyl acetate and dichloromethane, and the filtrate was evaporated to dryness. The crude was purified by flash chromatography (1:1 hexanes/ethyl acetate to 100% ethyl acetate) to give the title compound (0.105 g, 42%) as a solid.

Workup

  1. temperatureSubsequently, the reaction was cooled down
  2. filtrationfiltered through Celite®
  3. washeluting with ethyl acetate and dichloromethane
  4. customthe filtrate was evaporated to dryness
  5. customThe crude was purified by flash chromatography (1:1 hexanes/ethyl acetate to 100% ethyl acetate)

Sources & evidence

ORD record
ord-81c13cc09ee94a4f920e668d941e4131
Source dataset
uspto-grants-2015_09
Patent number
US09133200B2

Reaction notes

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