Potassium Carbonate → Tert-butyl 4-[2-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrimidin-5-yl]phenylcarbamate

HRID 969993Notes

Reaction equation

HRID 969993 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:11]12[CH2:16][CH2:15][CH:14]([CH2:13][CH2:12]1)[CH:9]([O:8][C:5]1[N:4]=[CH:3][C:2]([C:25]3[CH:26]=[CH:27][C:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[CH:29][CH:30]=3)=[CH:7][N:6]=1)[CH2:10]2

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2734617tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 210726093-((5-Bromopyrimidin-2-yl)oxy)quinuclidine

Product 1

HCID 69433847Tert-butyl 4-[2-(1-azabicyclo[2.2.2]oct-3-yloxy)pyrimidin-5-yl]phenylcarbamate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

The product of Example 18A (283 mg, 1 mmol) in tetrahydrofuran (anhydrous, 10 mL) was treated with t-butyl [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-carbamate (Frontier, 319 mg, 1 mmol), Pd2(dba)3 (Strem Chemicals, 24 mg, 0.025 mmol), (tBu3P)2Pd (Strem Chemicals, 26 mg, 0.05 mmol), K2CO3 (Aldrich, 276 mg 2 mmol) and heated at 60° C. under N2 for 15 hours. The resulting mixture was allowed to cool to room temperature, diluted with ethyl acetate (20 mL), and washed with brine (2×5 mL). The organic phase was concentrated and the title product was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.20) as a solid (340 mg, yield, 86%). 1H NMR (300 MHz, MeOH-d4) δ 1.48-1.63 (m, 10H), 1.65-1.91 (m, 2H), 2.02-2.16 (m, 1H), 2.22-2.30 (m, 1H), 2.75-3.05 (m, 5H), 3.36-3.48 (m, 1H), 5.13-5.21 (m, 1H), 7.54 (s, 4H), 8.78 (s, 2H) ppm. MS (DCl/NH3) m/z 397 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with brine (2×5 mL)
  3. concentrationThe organic phase was concentrated
  4. customthe title product was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.20) as a solid (340 mg, yield, 86%)

Sources & evidence

ORD record
ord-b610cc358d4d4a3b94c13ac91819db4f
Source dataset
uspto-grants-2007_12
Patent number
US07309699B2

Reaction notes

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