2-Amino-4-difluoromethyl-5-iodo-benzoic acid methyl ester → 2-Amino-4-difluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

HRID 1441621노트

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HRID 1441621 반응식
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8](I)[C:7]([CH:11]([F:13])[F:12])=[CH:6][C:5]=1[NH2:14].[CH:16]([N:19]1[C:23]([Sn](CCCC)(CCCC)CCCC)=[CH:22][CH:21]=[N:20]1)([CH3:18])[CH3:17]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[C:8]([C:23]2[N:19]([CH:16]([CH3:18])[CH3:17])[N:20]=[CH:21][CH:22]=2)[C:7]([CH:11]([F:13])[F:12])=[CH:6][C:5]=1[NH2:14]

참가 물질

5

반응물 2

HCID 591644452-Amino-4-difluoromethyl-5-iodo-benzoic acid methyl esterHCID 591645211-Isopropyl-5-tributylstannanyl-1H-pyrazole

생성물 1

HCID 591644772-Amino-4-difluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester수율 54%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

To a solution of 2-amino-4-difluoromethyl-5-iodo-benzoic acid methyl ester (750 mg, 2.29 mmol) in dioxane (30 mL) were added 1-isopropyl-5-tributylstannanyl-1H-pyrazole (1.1 g, 1.2 equiv) and Pd(dppf)2Cl2 (187 mg, 0.1 equiv) and the resulting mixture was stirred at 90° C. for 18 h. Another portion of catalyst (0.1 equiv) was added and the mixture was stirred at 90° C. for an additional 6 h. The solvent was removed in vacuo to afford a dark oil. The crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:100 to 30:70)) to provide the title compound as an off-white solid (380 mg, 54%). ES-MS: m/z 310.3 [M+H]+, rt 5.54 min.

후처리

  1. stirringthe mixture was stirred at 90° C. for an additional 6 h
  2. customThe solvent was removed in vacuo
  3. customto afford a dark oil
  4. customThe crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (0:100 to 30:70))

출처 및 근거

ORD 기록
ord-1eba0badcd7a495080dc7721c1502d54
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07655666B2

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