Phosphine → HCID 66869321, compound

HRID 1992643Notes

Reaction equation

HRID 1992643 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:9]([O:13][C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18](Cl)[CH:17]=1)([CH3:12])([CH3:11])[CH3:10].[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.P>COCCOC.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].C(P([C-]1C=CC=C1)C(C)(C)C)(C)(C)C.C1(C2[C-](C3C=CC=CC=3)C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C=2C2C=CC=CC=2)C=CC=CC=1.[Fe+2].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]>[C:9]([O:13][C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[C:18]([N:28]2[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]2)[CH:17]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

9

Reactant 4

HCID 24404Phosphine2×HCID 531671-MethylpiperazineHCID 62657Potassium Phosphate, TribasicHCID 86623474HCID 86623474, compound

Product 1

HCID 66869321HCID 66869321, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 72499888Dibenzalacetone palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Potassium phosphate (2.65 g, 12.47 mmol) is dried at 120° C. under high vacuum for 45 minutes. After cooling to RT and venting with dry argon, palladium dibenzylideneacetone (Pd2(dba)3, 25 mg, 0.03 mmol) and di-tert-butylphosphino pentaphenylferrocene (39 mg, 0.06 mmol) are added. (2-Chloro-pyridin-4-yl)-acetic acid tert-butyl ester (631 mg, 2.77 mmol), dissolved in 1,2-dimethoxyethane (14 ml, dried by passing through a column of basic aluminum oxide), and 1-methyl piperazine (830 mg, 8.31 mmol) are added. The reaction mixture is warmed to 40° C. for 1 h. Additional Pd2(dba)3 (25 mg, 0.03 mmol) and phosphine ligand (39 mg, 0.06 mmol) is added, and stirring is continued at 60° C. for 2 h. Additional Pd2(dba)3 (25 mg, 0.03 mmol) and phosphine ligand (39 mg, 0.06 mmol) is added, and stirring is continued at 90° C. for 18 h and at RT for 72 h. TLC and MS analysis indicated the presence of desired product. The reaction mixture is diluted with EtOAc and poured into a saturated solution of NaCl in water. The organic layer is separated, dried over Na2SO4, and the solvent is evaporated. Purification of the residue by FCC (hexane/EtOAc, gradient from 95:5 to 90:10) affords the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.44 (s, 9H), 2.34 (s, 3H), 2.52 (m, 4H), 3.42 (s, 2H), 3.55 (m, 4H), 6.55 (d, J=4 Hz, 1H), 6.56 (s, 1H), 8.11 (d, J=4 Hz, 1H). ES+−MS: 292.4 [M+H]+.

Workup

  1. customdried
  2. additionare added
  3. temperatureThe reaction mixture is warmed to 40° C. for 1 h
  4. stirringstirring
  5. waitis continued at 90° C. for 18 h and at RT for 72 h

Sources & evidence

ORD record
ord-f945637e8d154071a73c6f9645aceb1f
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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