Potassium Phosphate, Tribasic → 4-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 547917

Reaction equation

HRID 547917 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5](C2C=CC=CC=2)=[N:6][CH:7]=1.[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(N(CC)C(=O)C1C(=CC=CC=1)O)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Cu]I>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([NH:27][C:2]2[CH:7]=[N:6][CH:5]=[N:4][CH:3]=2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 88006DiethylsalicylamideHCID 12682914-Amino-1-Boc-piperidineHCID 143877455-Bromo-2-phenylpyrimidine

Product 1

HCID 671982114-(Pyrimidin-5-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 47.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-bromo-2-phenyl-pyrimidine (3.50 g, 14.89 mmol, 1.0 equiv), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.48 g, 22.33 mmol, 1.5 equiv), copper(I) iodide (0.28 g, 1.49 mmol, 0.1 equiv), N,N-diethylsalicylamide (0.58 g, 2.98 mmol, 0.2 equiv) and K3PO4 (3.16 g, 14.89 mmol, 1.0 equiv) in degassed DMF (30 mL) was heated under Ar to 90° C. for 24 h. The solvent was removed under reduced pressure and the crude reaction product extracted from water (300 mL) and 25% NH4OH (30 mL) with ethyl acetate (3×300 mL). The combined organic phases were dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography eluting with a gradient of heptane/ethyl acetate (4:1→1:1) to provide 1.98 g (38%) of the title compound. MS (ESI): 377.1 [M+Na]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe crude reaction product
  3. extractionextracted from water (300 mL) and 25% NH4OH (30 mL) with ethyl acetate (3×300 mL)
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationconcentrated by evaporation under reduced pressure
  6. customthe crude material purified by silica column chromatography
  7. washeluting with a gradient of heptane/ethyl acetate (4:1→1:1)

Sources & evidence

ORD record
ord-2a7eace60b054b44a3243b176692773e
Source dataset
uspto-grants-2011_05
Patent number
US07939661B2

Linked notes

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