Potassium Hydroxide → 4-(5-Morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1370045Notes

Reaction equation

HRID 1370045 reaction equation
[N:1]1([C:7]2[CH:8]=[C:9]3[CH:15]=[CH:14][NH:13][C:10]3=[CH:11][N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].[OH-].[K+].C([O-])=O.[NH4+]>CO.[Pd].CO.C(Cl)Cl>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([C:15]2[C:9]3[C:10](=[CH:11][N:12]=[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)[CH:8]=3)[NH:13][CH:14]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2723923Ammonium formateHCID 223120045-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridine

Product 1

HCID 691828124-(5-Morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent2×

Conditions

Temperature
65 °C

Procedure

A solution of 200 mg (1.0 mmol) of 5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridine and 398 mg (2.0 mmol, 2 eq) of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester in 5 mL of MeOH was treated with 224 mg (4.0 mmol, 4 eq) of potassium hydroxide. The reaction mixture was stirred at 65° C. for 12 h and volatiles were removed. The crude product was partitioned between CH2Cl2 (100 mL) and 20 mL of H2O. The organic layer was washed with H2O (2×20 mL), dried over Na2SO4 and concentrated. The yellow powder was treated with 630 mg (10 mmol, 10 eq) of ammonium formate and 10% Pd—C (50 mg). The reaction mixture was stirred at 65° C. for 1 h. The reaction mixture was then filtered through a pad of celite and concentrated to obtain a yellow solid. Column chromatography (silica, 5% MeOH/CH2Cl2) provided 180 mg (47% for 2 steps) of a yellow solid. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.40. MS (electrospray): exact mass calculated for C21H30N4O3, 386.23; m/z found, 387.2 [M+H]+.

Workup

  1. customvolatiles were removed
  2. customThe crude product was partitioned between CH2Cl2 (100 mL) and 20 mL of H2O
  3. washThe organic layer was washed with H2O (2×20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. stirringThe reaction mixture was stirred at 65° C. for 1 h
  7. filtrationThe reaction mixture was then filtered through a pad of celite
  8. concentrationconcentrated
  9. customto obtain a yellow solid

Sources & evidence

ORD record
ord-b6a32138e3c346efb199597a167d9b5a
Source dataset
uspto-grants-2003_06
Patent number
US06579896B2

Reaction notes

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