Potassium Carbonate → 5-{[1-(cyclopropylcarbonyl)-3-azetidinyl]methyl}-4-[4-(1H-indazol-6-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525189노트

반응식

HRID 525189 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][CH:14]3[CH2:17][N:16]([C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:23])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]3[C:38](=[CH:39][CH:40]=2)[NH:37][N:36]=[CH:35]3)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C>[CH:20]1([C:18]([N:16]2[CH2:17][CH:14]([CH2:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:40]5[CH:39]=[C:38]6[C:34]([CH:35]=[N:36][NH:37]6)=[CH:33][CH:32]=5)=[CH:3][CH:4]=4)[C:9](=[O:23])[NH:10][N:11]=3)[CH2:15]2)=[O:19])[CH2:22][CH2:21]1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 177504691H-Indazole-5-boronic acid pinacol esterHCID 673551434-(4-bromophenyl)-5-{[1-(cyclopropylcarbonyl)-3-azetidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

생성물 1

HCID 673758655-{[1-(cyclopropylcarbonyl)-3-azetidinyl]methyl}-4-[4-(1H-indazol-6-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one수율 26%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

In a microwave vial purged with nitrogen, a mixture of 4-(4-bromophenyl)-5-{[1-(cyclopropylcarbonyl)-3-azetidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (70 mg, 0.186 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (8 mg, 9.80 μmol), and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (50 mg, 0.205 mmol)) in 1,4-dioxane (2 mL) and 2M aq potassium carbonate (0.7 mL, 1.400 mmol) was stirred at 100° C. in an oil bath for 16 h. The reaction was cooled to room temperature and diluted with ethyl acetate (10 mL). The layers were separated and the aqueous layer was adjusted to pH˜6-6.5 using 1N aq HCl. The aqueous layer was extracted with ethyl acetate (2×30 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. Purification of the residue by reverse phase HPLC (10-90% acetonitrile/water+0.1% NH4OH) provided the title compound as a white solid (20 mg, 26%). MS(ES)+ m/e 415.2 [M+H]+.

후처리

  1. customIn a microwave vial purged with nitrogen
  2. customThe layers were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by reverse phase HPLC (10-90% acetonitrile/water+0.1% NH4OH)

출처 및 근거

ORD 기록
ord-730c2beee8174cafa73a16135579f875
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340529B2

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