Binap, (A+-)- → 4-({2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carbonitrile

HRID 1776428노트

반응식

HRID 1776428 반응식
[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([O:21][CH3:22])=[CH:16][N:15]=2)=[N:6]1.Br[C:28]1[CH:33]=[CH:32][N:31]=[CH:30][C:29]=1[C:34]#[N:35].C1(C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C(=CC=CC=2)C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])(C)C.[Na+]>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].CN(C)C=O>[F:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH:20][C:28]3[CH:33]=[CH:32][N:31]=[CH:30][C:29]=3[C:34]#[N:35])[C:17]([O:21][CH3:22])=[CH:16][N:15]=2)=[N:6]1

참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 223295224-Bromopyridine-3-carbonitrileHCID 23676156Sodium t-butoxideHCID 867324252-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine

생성물 1

HCID 867324544-({2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carbonitrile

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매

실험 절차

175 mg of 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine (1-11-1, 0.501 mmol, 1. eq.), 101 mg of 4-bromopyridine-3-carbonitrile (0.551 mmol, 1.1 eq.), 115 mg of Tris(dibenzylideneacetone)dipalladium (0) (0.125 mmol, 0.25 eq.), 156 mg of 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.25 mmol, 0.5 eq), 144 mg of sodium 2-methylpropan-2-olate (97%) (1.503 mmol, 3 eq.) and 52 ml of N,N-dimethylformamide were stirred under nitrogen atmosphere for 30 minutes at 100° C. and 300 W in a CEM microwave. The reaction mixture was washed with half-saturated aqueous sodium chloride solution. The organic layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (hexane/dichloromethane/methanol) and preparative HPLC. A crystallisation from dichloromethane/methanol gave 5.8 mg (0.01 mmol, 2.6%) of the analytically pure target compound.

후처리

  1. washThe reaction mixture was washed with half-saturated aqueous sodium chloride solution
  2. extractionThe organic layer was extracted twice with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (hexane/dichloromethane/methanol) and preparative HPLC
  7. customA crystallisation from dichloromethane/methanol
  8. customgave 5.8 mg (0.01 mmol, 2.6%) of the analytically pure target compound

출처 및 근거

ORD 기록
ord-e5ed52edc03240d4961df295345bb194
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09265763B2

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