2,6-Lutidine → N-[6-Amino-5-(2-chloro-5-methoxyphenyl)pyridin-2-yl]-1-ethyl-1H-pyrazole-5-carboxamide

HRID 1094786

반응식

HRID 1094786 반응식
[CH2:1]([N:3]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[N:4]1)[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=1[C:26]1[C:27]([NH2:33])=[N:28][C:29]([NH2:32])=[CH:30][CH:31]=1.N1C(C)=CC=CC=1C>ClCCl.O1CCCC1.CN(C)C=O.C(#N)C>[NH2:33][C:27]1[N:28]=[C:29]([NH:32][C:8]([C:7]2[N:3]([CH2:1][CH3:2])[N:4]=[CH:5][CH:6]=2)=[O:10])[CH:30]=[CH:31][C:26]=1[C:19]1[CH:20]=[C:21]([O:24][CH3:25])[CH:22]=[CH:23][C:18]=1[Cl:17]

참가 물질

9

반응물 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 5657021-Ethyl-1H-pyrazole-5-carboxylic acidHCID 575823413-(2-Chloro-5-methoxyphenyl)pyridine-2,6-diamine

생성물 1

HCID 25159328N-[6-Amino-5-(2-chloro-5-methoxyphenyl)pyridin-2-yl]-1-ethyl-1H-pyrazole-5-carboxamide수율 20.2%

시약·촉매·용매 4

HCID 6228Dimethylformamide촉매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To an ice-cooled solution of 1-ethyl-1H-pyrazole-5-carboxylic acid (0.140 g, 1 mmol) in dichloromethane (2 ml) and tetrahydrofuran (2 ml) was added oxalyl chloride (0.262 ml, 3 mmol) followed by 1 drop of dimethylformamide. The reaction was stirred at room temperature for 1 hour before concentration in vacuo. The residue was azeotroped with dichloromethane, dissolved in acetonitrile (4 ml) and 2 ml was added dropwise to a cooled solution of 3-(2-chloro-5-methoxyphenyl)pyridine-2,6-diamine (preparation 1, 0.100 g, 0.4 mmol) and lutidine (0.070 ml, 0.6 mmol) in acetonitrile (4 ml). The reaction was allowed to warm to room temperature and stirred under nitrogen for 72 hours. The reaction was concentrated in vacuo and partitioned between dichloromethane (10 ml) and water (10 ml). The organic was dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with ethylacetate:heptane 1:3 to 3:1 to furnish 30 mg white solid as the desired compound.

후처리

  1. customThe residue was azeotroped with dichloromethane
  2. dissolutiondissolved in acetonitrile (4 ml)
  3. temperatureto warm to room temperature
  4. stirringstirred under nitrogen for 72 hours
  5. concentrationThe reaction was concentrated in vacuo
  6. custompartitioned between dichloromethane (10 ml) and water (10 ml)
  7. dry with materialThe organic was dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel column chromatography
  10. washeluting with ethylacetate:heptane 1:3 to 3:1

출처 및 근거

ORD 기록
ord-c9b7d41d2119439b89cf46c2b9a9de1a
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08134007B2

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