Potassium Phosphate, Tribasic → 1-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester

HRID 631916노트

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HRID 631916 반응식
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:9]([O:11][C:12](=[O:27])[NH:13][C:14]2[N:15]([CH3:26])[N:16]=[N:17][C:18]=2[C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)[CH3:10])[CH:6]=[CH:7][CH:8]=1.CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][C:41]([C:44]3([C:47]([O:49][CH3:50])=[O:48])[CH2:46][CH2:45]3)=[CH:40][CH:39]=2)O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:50][O:49][C:47]([C:44]1([C:41]2[CH:42]=[CH:43][C:38]([C:22]3[CH:23]=[CH:24][C:19]([C:18]4[N:17]=[N:16][N:15]([CH3:26])[C:14]=4[NH:13][C:12]([O:11][CH:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:29])([F:28])[F:1])[CH:4]=4)[CH3:10])=[O:27])=[CH:20][CH:21]=3)=[CH:39][CH:40]=2)[CH2:46][CH2:45]1)=[O:48]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 71264507Methyl 1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropane-1-carboxylateHCID 118062436[5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester

생성물 1

HCID 1180627761-(4'-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester수율 53.3%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
95 °C

실험 절차

[5-(4-Bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid 1-(3-trifluoromethyl-phenyl)-ethyl ester (680 mg, 1.45 mmol), methyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (525 mg, 1.74 mmol), X-Phos (138 mg, 0.29 mmol), palladium acetate (33 mg, 0.14 mmol) and potassium phosphate tribasic (923 mg, 4.35 mmol) were mixed in toluene (10 mL). Degassed water (2 mL) was added and the mixture was degassed with argon and then sealed. The mixture was stirred at 95° C. for 5 hrs until all starting material was consumed. The mixture was extracted with ethyl acetate and water. The organic layer was washed with brine and dried. Solvents were evaporated and the residue was purified by flash column chromatography (ethyl acetate in hexanes 5% to 70% in 15 minutes, 40 g silica gel) to give an amorphous white fluffy material as 1-(4′-{1-methyl-5-[1-(3-trifluoromethyl-phenyl)-ethoxycarbonylamino]-1H-[1,2,3]triazol-4-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid methyl ester (436 mg, 53.3% yield). LC/MS calcd for C30H27F3N4O4 (m/e) 564.0, obsd 565.0 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.18-1.35 (m, 2.6H), 1.48-1.55 (m, 2H), 1.60 (br d, J=3.8 Hz, 2.4H), 3.57 (s, 3H), 3.86 (s, 3H), 5.80-5.90 (br m, 1H), 7.44 (d, J=8.3 Hz, 2.5H), 7.63 (d, J=8.1 Hz, 2.5H), 7.69 (br d, J=7.3 Hz, 3.5H), 7.80 (d, J=7.3 Hz, 3.5H), 9.65 and 10.06 (br s, 1H).

후처리

  1. customthe mixture was degassed with argon
  2. customsealed
  3. customwas consumed
  4. extractionThe mixture was extracted with ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. customdried
  7. customSolvents were evaporated
  8. customthe residue was purified by flash column chromatography (ethyl acetate in hexanes 5% to 70% in 15 minutes, 40 g silica gel)

출처 및 근거

ORD 기록
ord-c585224eb85a41e5afba39abf2a14b7c
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321738B2

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