Tolylboronic acid → Methyl 2-(4-ethyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate

HRID 1399739Notes

Reaction equation

HRID 1399739 reaction equation
Cl[C:2]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH2:16][CH3:17])[N:5]=[C:4]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[N:3]=1.B(O)(O)[C:25]1[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=1.C(N(CC)C(C)C)(C)C>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:16]([C:6]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:2]([C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)[N:3]=[C:4]([N:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)[N:5]=1)[CH3:17]

Participants

7

Reactant 3

HCID 79799Tolylboronic acidHCID 81531DiisopropylethylamineHCID 86665657Methyl 2-(4-chloro-6-ethyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

Product 1

HCID 66955305Methyl 2-(4-ethyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoateYield 38.4%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

methyl 2-(4-chloro-6-ethyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate (0.190 g; 0.559 mmol), p-tolylboronic acid (114 mg; 0.839 mmol), tetrakis(triphenylphosphine) palladium(0) (64.6 mg; 0.056 mmol) were placed in a 5 mL reaction tube and dissolved in a mixture of degassed DME (1.50 mL) and water (0.5 mL). N,N-Diisopropylethylamine (0.344 mL; 2.236 mmol) was added, the tube was sealed and irradiated in a microwave oven at 130° C. for 30 min. The reaction mixture was partitioned between brine and dichloromethane, filtered over a phase separator filter (1PS) and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (2-20%) in heptane to give 85 mg (35%) of the title compound as a yellow oil.

Workup

  1. customthe tube was sealed
  2. customirradiated in a microwave oven at 130° C. for 30 min
  3. customThe reaction mixture was partitioned between brine and dichloromethane
  4. filtrationfiltered over a phase separator
  5. filtrationfilter (1PS)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (2-20%) in heptane

Sources & evidence

ORD record
ord-5f39dd70323e4c1d8259d8962d8793a1
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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