O-Xylene → Imatinib

HRID 1160127

반응식

HRID 1160127 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[N:8]=2)[CH:2]=1.Br[C:15]1[CH:16]=[C:17]([NH:22][C:23](=[O:38])[C:24]2[CH:29]=[CH:28][C:27]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[CH:26][CH:25]=2)[CH:18]=[CH:19][C:20]=1[CH3:21].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C(C)=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:37][N:34]1[CH2:33][CH2:32][N:31]([CH2:30][C:27]2[CH:28]=[CH:29][C:24]([C:23]([NH:22][C:17]3[CH:16]=[CH:15][C:20]([CH3:21])=[C:19]([NH:13][C:9]4[N:8]=[C:7]([C:3]5[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=5)[CH:12]=[CH:11][N:10]=4)[CH:18]=3)=[O:38])=[CH:25][CH:26]=2)[CH2:36][CH2:35]1

참가 물질

7

반응물 4

HCID 7237O-XyleneHCID 634876Binap, (A+-)-HCID 10309714N-(3-bromo-4-methyl-phenyl)4-(4-methyl-piperazin-1-ylmethyl)-benzamideHCID 124505824-(Pyridin-3-yl)pyrimidin-2-amine

생성물 1

HCID 5291Imatinib

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매

실험 절차

To a mixture of 4-(3-pyridyl)-2-pyrimidine-amine (172.2 mg, 1.0 mmol), N-(3-bromo-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide (402.4 mg, 1.0 mmol) and sodium tert.-butylate (144.2 mg, 1.5 mmol) is added a mixture of rac-BINAP (31.2 mg, 0.050 mmol) and Pd2(dba)3*CHCl3 (13 mg, 0.013 mmol) under argon. After addition of 3 ml of xylene the suspension is sonicated for 10 minutes then stirred for 5 hours under reflux. After cooling to room temperature, water (10 ml) is added to the dark brown oil and the product extracted 4 times with methylene chloride (10 ml each). The combined organic extracts are dried over MgSO4 and concentrated in vacuo. The brown oil is purified by flash-chromatography (SiO2, methanol). The product, a pale yellow solid is dissolved in methylene chloride, filtered and concentrated in vacuo. Yield: 484.3 mg of the title compound, 72% of theory, (99.9% area by HPLC). The product contains typically roughly 10% of isomers which can be eliminated by preparative reversed phase chromatography.

후처리

  1. additionis added
  2. customis sonicated for 10 minutes
  3. temperatureunder reflux
  4. extractionthe product extracted 4 times with methylene chloride (10 ml each)
  5. dry with materialThe combined organic extracts are dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe brown oil is purified by flash-chromatography (SiO2, methanol)
  8. dissolutionThe product, a pale yellow solid is dissolved in methylene chloride
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-214efff2b2f54554ba7e8db81d7bc8d6
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07816359B2

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