Potassium Carbonate → 6-Bromo-2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazole

HRID 1429547Notes

Reaction equation

HRID 1429547 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([CH2:9][CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[O:8][C:4]=2[CH:3]=1.Cl[C:19]1[N:24]=[CH:23][C:22]([CH2:25][CH2:26][CH3:27])=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([CH2:9][CH:10]3[CH2:11][CH2:12][N:13]([C:19]4[N:24]=[CH:23][C:22]([CH2:25][CH2:26][CH3:27])=[CH:21][N:20]=4)[CH2:14][CH2:15]3)[O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27357842-Chloro-5-propylpyrimidineHCID 674662846-Bromo-2-(piperidin-4-ylmethyl)benzo[d]oxazole

Product 1

HCID 674649446-Bromo-2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazoleYield 83.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-bromo-2-(piperidin-4-ylmethyl)benzo[d]oxazole (0.13 g, 0.440 mmol), 2-chloro-5-propylpyrimidine (0.083 g, 0.529 mmol), and K2CO3 (0.122 g, 0.881 mmol) in DMF (4.4 mL) was heated in 90° C. oil bath for 12 h. It was cooled to rt, quenched with H2O (5 mL), and extracted with EtOAc-Et2O (3×4 mL, 1:1 v/v). The combined organic layers were washed with H2O (3×4 mL) and brine (4 mL). The solvent was evaporated to afford crude product, which was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0-60% EtOAc) to afford the desired product as a colorless oil (153 mg, 83% yield). 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 2H), 7.66 (d, J=1.8 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.43 (dd, J=8.4, 1.8 Hz, 1H), 4.73 (d, J=13.4 Hz, 2H), 3.04-2.77 (m, 4H), 2.48-2.32 (m, 2H), 2.24 (s, 1H), 1.85 (d, J=12.6 Hz, 2H), 1.67-1.49 (m, 2H), 1.37 (ddd, J=25.0, 12.4, 4.2 Hz, 2H), 0.92 (t, J=7.3 Hz, 3H). LCMS (m/z)=415 (M+H)+.

Workup

  1. temperatureIt was cooled to rt
  2. customquenched with H2O (5 mL)
  3. extractionextracted with EtOAc-Et2O (3×4 mL, 1:1 v/v)
  4. washThe combined organic layers were washed with H2O (3×4 mL) and brine (4 mL)
  5. customThe solvent was evaporated
  6. customto afford crude product, which
  7. customwas purified by column chromatography (silica gel, hexanes-EtOAc gradient 0-60% EtOAc)

Sources & evidence

ORD record
ord-df2e764ca28f49ad8250314bd87bd8ff
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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