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

HRID 446517노트

반응식

HRID 446517 반응식
[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]

참가 물질

9

반응물 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, 화합물3회

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매3회HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매3회HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-49ac81542bfe475a9a4f1d78e5fbd54e
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476253B2

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