Potassium Carbonate → tert-Butyl 4-(2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazol-6-yl)-5,6-dihydropyridine-1 (2H)-carboxylate

HRID 1429548Notes

Reaction equation

HRID 1429548 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]2[N:6]=[C:7]([CH2:9][CH:10]3[CH2:15][CH2:14][N:13]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][CH2:23][CH3:24])=[CH:18][N:17]=4)[CH2:12][CH2:11]3)[O:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([C:19]1[CH:18]=[N:17][C:16]([N:13]2[CH2:14][CH2:15][CH:10]([CH2:9][C:7]3[O:8][C:4]4[CH:3]=[C:2]([C:35]5[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=5)[CH:26]=[CH:25][C:5]=4[N:6]=3)[CH2:11][CH2:12]2)=[N:21][CH:20]=1)[CH2:23][CH3:24]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 674649446-Bromo-2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazole

Product 1

HCID 68208557tert-Butyl 4-(2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazol-6-yl)-5,6-dihydropyridine-1 (2H)-carboxylateYield 96.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 6-bromo-2-((1-(5-propylpyrimidin-2-yl)piperidin-4-yl)methyl)benzo[d]oxazole (0.15 g, 0.361 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.156 g, 0.506 mmol) and K2CO3 (0.125 g, 0.903 mmol) in dioxane (3.7 mL) and water (1.2 mL) was added Pd(Ph3P)4 (0.021 g, 0.018 mmol). The reaction mixture was stirred at 100° C. for 15 h. The reaction mixture was cooled to rt, and diluted with EtOAc/Ether (10 mL, 1:1 v/v). The organic layer was washed with NaHCO3 (aq, sat, 6 mL) and NaCl (saturated aqueous, 6 mL). It was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc) to afford desired product as a light yellow solid (180 mg, 96% yield). 1H NMR (400 MHz, chloroform-d) δ 8.14 (s, 2H), 7.61 (d, J=8.3 Hz, 1H), 7.47 (d, J=1.3 Hz, 1H), 7.38-7.33 (m, 1H), 6.15-5.95 (m, 2H), 4.73 (d, J=13.4 Hz, 1H), 4.10 (s, 2H), 3.67 (t, J=5.6 Hz, 3H), 2.99-2.79 (m, 3H), 2.57 (s, 2H), 2.46-2.33 (m, 2H), 2.32-2.13 (m, 2H), 1.87 (d, J=11.2 Hz, 2H), 1.63-1.53 (m, 1H), 1.50 (s, 9H), 1.37 (dd, J=12.5, 4.0 Hz, 2H), 0.93 (t, J=7.3 Hz, 3H). LCMS (m/z)=518 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. washThe organic layer was washed with NaHCO3 (aq, sat, 6 mL) and NaCl (saturated aqueous, 6 mL)
  3. dry with materialIt was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc)

Sources & evidence

ORD record
ord-5b79b1b0f15d4a4b89f8e82fba541a47
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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