Diisopropylethylamine → HCID 66956045, compound

HRID 1399715Notes

Reaction equation

HRID 1399715 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]([CH3:16])[N:5]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[N:3]=1.C(N(CC)C(C)C)(C)C.[Cl:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[C:35]([F:42])[CH:34]=1>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>[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:16])[N:5]=[C:4]([N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[N:3]=2)=[C:35]([F:42])[CH:34]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86665653Methyl 2-(4-chloro-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate

Product 1

HCID 66956045HCID 66956045, compoundYield 46.7%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of methyl 2-(4-chloro-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate (0.081 g; 0.25 mmol), tetrakis(triphenylphosphine) palladium(0) (0.029 g; 0.025 mmol), N,N-diisopropylethylamine (0.172 mL; 1.00 mmol) and 4-chloro-2-fluorophenylboronic acid (0.065 g; 0.375 mmol) in a mixture of DME-water (3:1, 1 mL) was heated at 100° C. for 2.5 h. The mixture was partitioned between brine and dichloromethane, filtered over a phase separator filter (1PS) and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane furnished 0.049 g (38%) of the title compound as a colorless oil.

Workup

  1. customThe mixture was partitioned between brine and dichloromethane
  2. filtrationfiltered over a phase separator
  3. filtrationfilter (1PS)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane

Sources & evidence

ORD record
ord-9c8ef0f398964693a1c2826f79e99917
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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