2,5-Dioxopyrrolidin-1-yl (4-methylbenzyl) carbonate → 4-[(3-Methoxy-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid 4-methyl-benzyl ester

HRID 1827221Notes

Reaction equation

HRID 1827221 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[N:5][CH:6]=[CH:7][N:8]=1.[CH3:17][C:18]1[CH:35]=[CH:34][C:21]([CH2:22][O:23][C:24](=O)[O:25]N2C(=O)CCC2=O)=[CH:20][CH:19]=1>CN(C=O)C.C(OCC)(=O)C>[CH3:17][C:18]1[CH:35]=[CH:34][C:21]([CH2:22][O:23][C:24]([N:14]2[CH2:15][CH2:16][CH:11]([CH2:10][NH:9][C:4]3[C:3]([O:2][CH3:1])=[N:8][CH:7]=[CH:6][N:5]=3)[CH2:12][CH2:13]2)=[O:25])=[CH:20][CH:19]=1

Participants

5

Reactant 2

HCID 111399512,5-Dioxopyrrolidin-1-yl (4-methylbenzyl) carbonate2×HCID 221357494-[(3-Methoxy-pyrazin-2-ylamino)-methyl]-piperidine

Product 1

HCID 235773024-[(3-Methoxy-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid 4-methyl-benzyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-[(3-methoxy-pyrazin-2-ylamino)-methyl]-piperidine (EXAMPLE 127, STEP 3) (0.093 g, 0.00042 mol) and N-(4-methylbenzyloxycarbonyloxy)succinimide (INTERMEDIATE 1A)(118 mg) in DMF (2 mL) was stirred at rt for 18 h. The reaction was diluted with ethyl acetate (30 mL), washed with 10% aqueous sodium bicarbonate (20 mL) followed by brine (10 mL), concentrated in vacuo and chromatographed on silica using a gradient elution of 5–15% acetone/dichloromethane. Concentration in vacuo followed by crystallization from ether/hexane gave the title compound. M.S.(M+1): 371.

Workup

  1. washwashed with 10% aqueous sodium bicarbonate (20 mL)
  2. concentrationconcentrated in vacuo
  3. customchromatographed on silica using
  4. washa gradient elution of 5–15% acetone/dichloromethane
  5. concentrationConcentration in vacuo
  6. customfollowed by crystallization from ether/hexane

Sources & evidence

ORD record
ord-2503b9f260424f8da40982c0e4e88e77
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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