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

HRID 631918노트

반응식

HRID 631918 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][N:11]([CH3:22])[C:12]=2[NH:13][C:14](=[O:21])[O:15][C@@H:16]([CH:18]([CH3:20])[CH3:19])[CH3:17])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][C:34]([C:37]3([C:40]([O:42][CH3:43])=[O:41])[CH2:39][CH2:38]3)=[CH:33][CH:32]=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>[CH3:43][O:42][C:40]([C:37]1([C:34]2[CH:35]=[CH:36][C:31]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[N:9]=[N:10][N:11]([CH3:22])[C:12]=4[NH:13][C:14]([O:15][C@H:16]([CH3:17])[CH:18]([CH3:20])[CH3:19])=[O:21])=[CH:4][CH:3]=3)=[CH:32][CH:33]=2)[CH2:39][CH2:38]1)=[O:41]

참가 물질

7

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 118061596(R)-3-Methylbutan-2-yl 4-(4-bromophenyl)-1-methyl-1H-1,2,3-triazol-5-ylcarbamate

생성물 1

HCID 1180622341-{4'-[5-((R)-1,2-dimethyl-propoxycarbonylamino)-1-methyl-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester수율 76.6%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
95 °C

실험 절차

(R)-3-Methylbutan-2-yl 4-(4-bromophenyl)-1-methyl-1H-1,2,3-triazol-5-ylcarbamate (101.4 mg. 0.28 mmol), methyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (108 mg, 0.36 mmol), X-Phos (39.5 mg, 0.083 mmol), palladium acetate (9.3 mg, 0.041 mmol), and potassium phosphate tribasic (176 mg, 0.83 mmol) were combined in toluene (6 mL). To this mixture was added degassed water (1.5 mL) and the mixture was stirred at 95° C. for 2 hrs until it became black. LC/MS indicated no more starting material. 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 ISCO flash column chromatography (12 g silica gel, 5% to 65% ethyl acetate in hexanes) to give a pale yellow solid as 1-{4′-[5-((R)-1,2-dimethyl-propoxycarbonylamino)-1-methyl-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester (97.8 mg, 76.6% yield). LC/MS calcd for C26H30N4O4 (m/e) 462, obsd 463.2 (M+H).

후처리

  1. additionTo this mixture was added
  2. customdegassed water (1.5 mL)
  3. extractionThe mixture was extracted with ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. customdried
  6. customSolvents were evaporated
  7. customthe residue was purified by ISCO flash column chromatography (12 g silica gel, 5% to 65% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-4e045f724bc144db82df8bfa860ff191
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321738B2

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