Benzyl Alcohol → Benzyl 2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)pyrimidine-5-carboxylate

HRID 446517Notes

Reaction equation

HRID 446517 reaction equation
[C:1]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:35])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]2[N:32]=[CH:31][C:30](Br)=[CH:29][N:28]=2)[CH3:19])[CH2:12][CH2:11]1.C(N(CC)CC)C.[CH2:49]([OH:56])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.[C]=O.CN(C)[CH:61]=[O:62]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([CH3:19])[C:20](=[O:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]2[N:32]=[CH:31][C:30]([C:61]([O:56][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:62])=[CH:29][N:28]=2)[CH2:12][CH2:11]1)=[O:35]

Participants

9

Reactant 5

HCID 244Benzyl AlcoholHCID 6228DimethylformamideHCID 8471TriethylamineHCID 666715871-{2-[{6-[(5-Bromopyrimidin-2-yl)amino]hexanoyl}(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateHCID 178418416HCID 178418416, compound3×

Product 1

HCID 66671726Benzyl 2-({6-[(2-{4-[(biphenyl-2-ylcarbamoyl)oxy]piperidin-1-yl}ethyl)(methyl)amino]-6-oxohexyl}amino)pyrimidine-5-carboxylateYield 60%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst3×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

The compound (279 mg, 0.447 mmol) obtained in Example 14a was dissolved in N,N-dimethylformamide (3 mL), and palladium acetate (15 mg, 0.0671 mmol), 1,1′-bis(diphenylphosphino)ferrocene (74 mg, 0.134 mmol), triethylamine (1.24 mL, 8.94 mmol) and benzyl alcohol (0.926 mL, 8.94 mmol) were added. The atmosphere in the system was replaced with a carbon monoxide atmosphere, the mixture was stirred at 90° C. for 17.5 hours, then palladium acetate (30 mg, 0.134 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (148 mg, 0.268 mmol) were added, and the mixture was stirred at 90° C. under the carbon monoxide atmosphere for 29 hours. Palladium acetate (30 mg, 0.134 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (148 mg, 0.268 mmol) were added, and the mixture was stirred at 90° C. under the carbon monoxide atmosphere for 60 hours. The reaction mixture was diluted with ethyl acetate, insoluble matter was removed by filtration through celite, then the solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=1:1→1:2, v/v) to give the title compound (182 mg; yield, 60%) as a brown oily substance.

Workup

  1. customwas removed by filtration through celite
  2. customthe solvent was evaporated under reduced pressure
  3. customthe resulting residue was purified by NH silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-49ac81542bfe475a9a4f1d78e5fbd54e
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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