Cesium carbonate → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[2-fluoro-5-methyl-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525231노트

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HRID 525231 반응식
Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N:9]2[C:13]([CH2:14][C@@H:15]3[CH2:19][CH2:18][N:17]([C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[CH2:16]3)=[N:12][NH:11][C:10]2=[O:25])=[C:4]([F:26])[CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:44]=[C:43]3[C:38]([CH:39]=[CH:40][CH:41]=[N:42]3)=[CH:37][CH:36]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].ClCCl>[CH:22]1([C:20]([N:17]2[CH2:18][CH2:19][C@@H:15]([CH2:14][C:13]3[N:9]([C:5]4[CH:6]=[C:7]([CH3:8])[C:2]([C:35]5[CH:44]=[C:43]6[C:38]([CH:39]=[CH:40][CH:41]=[N:42]6)=[CH:37][CH:36]=5)=[CH:3][C:4]=4[F:26])[C:10](=[O:25])[NH:11][N:12]=3)[CH2:16]2)=[O:21])[CH2:24][CH2:23]1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 592961167-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)QuinolineHCID 710872904-(4-bromo-2-fluoro-5-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

생성물 1

HCID 682610065-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[2-fluoro-5-methyl-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one수율 84%

시약·촉매·용매 1

HCID 178418807HCID 178418807, 화합물촉매

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온도
100 °C

실험 절차

To a microwave vial were added 4-(4-bromo-2-fluoro-5-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.160 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.20 mmol), cesium carbonate (0.39 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (0.0062 mmol). The mixture was purged with nitrogen and suspended in 1,4-dioxane (1 mL) and water (0.5 mL). The mixture was heated for 15 h at 100° C. Analysis by LCMS indicated desired product formation and consumption of starting material. The mixture was filtered through a syringe filter and purified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA). The desired fractions were collected and added to a reparatory funnel containing ethyl acetate. The aqueous phase was adjusted to pH˜6 with 1N aq HCl. The aqueous phase was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over Na2SO4, and concentrated to afford the title product as a white solid (52 mg, 84%). MS(ES)+ m/e 472.2 [M+H]+.

후처리

  1. customThe mixture was purged with nitrogen
  2. customdesired product formation and consumption of starting material
  3. filtrationThe mixture was filtered through a syringe
  4. filtrationfilter
  5. custompurified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA)
  6. customThe desired fractions were collected
  7. additionadded to a reparatory funnel
  8. additioncontaining ethyl acetate
  9. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  10. washthe combined organics were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated

출처 및 근거

ORD 기록
ord-a7072f37b37a47e6aeefc71e4e1aebda
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340529B2

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