Piperidine → HCID 25121514, compound

HRID 2400584Notes

Reaction equation

HRID 2400584 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:13]3[CH:17]=[C:16]([CH3:18])[N:15]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=4)[N:14]=3)[O:11][CH:12]=2)=[CH:4][CH:3]=1.[NH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>COCCOC.[Pd](Cl)Cl>[CH3:18][C:16]1[N:15]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[N:14]=[C:13]([C:10]2[O:11][CH:12]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:3][CH:4]=3)[N:9]=2)[CH:17]=1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 62657Potassium Phosphate, TribasicHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 25121166HCID 25121166, compound

Product 1

HCID 25121514HCID 25121514, compoundYield 11.1%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4-(4-bromophenyl)-2-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,3-oxazole (Example 75, 150 mg, 0.37 mmol), piperidine (44 μl, 0.44 mmol), potassium phosphate (156 mg, 0.74 mmol), palladium(II) chloride (3.3 mg, 0.02 mmol) and 2-(dicyclohexylphosphino)-1,1′-biphenyl (9.7 mg, 0.03 mmol) in 1,2-dimethoxyethane (3 ml) was heated to reflux for 18 h. After cooling to rt, the mixture was filtered over a pad of celite. The filtrate was diluted with ethyl acetate and successively washed with 0.1 N aqueous HCl and water. The organic layer was dried (MgSO4), filtered and concentrated to dryness. The crude material was purified by preparative HPLC. The combined product fractions were then further purified by flash chromatography (silica) eluting with cyclohexane/ethyl acetate 5:1 to afford the title compound as a white solid (17 mg, 11%): 1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 7.63 (d, 2H), 7.17 (d, 2H), 7.08 (d, 2H), 6.98 (d, 2H), 6.65 (s, 1H), 5.35 (s, 2H), 3.19 (m, 4H), 2.28 (s, 6H), 1.64-1.52 (m, 6H); ES-MS m/z 413, HPLC RT (Method D) 2.65 min.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 18 h
  3. filtrationthe mixture was filtered over a pad of celite
  4. additionThe filtrate was diluted with ethyl acetate
  5. washsuccessively washed with 0.1 N aqueous HCl and water
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude material was purified by preparative HPLC
  10. customThe combined product fractions were then further purified by flash chromatography (silica)
  11. washeluting with cyclohexane/ethyl acetate 5:1

Sources & evidence

ORD record
ord-95203cd461e7485f9498a02c654e37e0
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

Loading…