Diisopropylethylamine → (R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate

HRID 2044037Notes

Reaction equation

HRID 2044037 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.Cl[C:16]1[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[O:21])=[C:18]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[O:33])=[CH:28][CH:27]=2)[N:17]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O.O>[C:10]([O:9][C:8](=[O:14])[NH:7][C@@H:3]1[CH2:4][CH2:5][CH2:6][N:1]([C:16]2[CH:24]=[CH:23][C:19]([C:20](=[O:21])[NH2:22])=[C:18]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)=[O:33])=[CH:28][CH:27]=3)[N:17]=2)[CH2:2]1)([CH3:11])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514172(3R)-3-Aminopiperidine, 3-BOC protectedHCID 574896016-Chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide

Product 1

HCID 49846385(R)-tert-butyl 1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamateYield 66.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of (R)-tert-butyl piperidin-3-ylcarbamate (416 mg, 2.079 mmol), 6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (500 mg, 1.386 mmol), and N,N-diisopropylethylamine (0.484 mL, 2.77 mmol) in N-methyl-2-pyrrolidinone (3 mL) was heated to 120° C. overnight. The reaction mixture was diluted with water. The grey precipitate was filtered and the solid was purified by chromatography (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g+12 g stack silica gel columns) to give 485 mg of (R)-tert-butyl-1-(5-carbamoyl-6-(4-(morpholine-4-carbonyl)phenylamino)pyridin-2-yl)piperidin-3-ylcarbamate as a yellow solid.

Workup

  1. filtrationThe grey precipitate was filtered
  2. customthe solid was purified by chromatography (ISCO, 5% NH4OH/MeOH/CH2Cl2, 40 g+12 g stack silica gel columns)

Sources & evidence

ORD record
ord-0583f5f7497d479696a70474ecfda070
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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