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Potassium Carbonate → Methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 604684
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HRID 604684 반응식
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42][CH3:43])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:49]1(B(O)O)[CH2:51][CH2:50]1.C([O-])([O-])=O.[K+].[K+]>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].C1COCC1>[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42][CH3:43])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:49]4[CH2:51][CH2:50]4)[N:21]=3)[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 57576282methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate2회

생성물 1

HCID 86627637Methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-cyclopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

시약·촉매·용매 2

HCID 178454861HCID 178454861, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

Methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (EXAMPLE 59 100 mg, 0.144 mmol), cyclopropylboronic acid (62.0 mg, 0.721 mmol), 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (19.62 mg, 0.029 mmol), aqueous K2CO3 (1M, 1.010 mL, 1.010 mmol) and THF (1.002 mL) were stirred at 80° C. for 3.5 h then slowly cooled to ambient overnight. Volatiles were removed under reduced pressure. The resulting pot residue was worked up with brine, extracted with EtOAc, dried (Na2SO4), filtered and evaporated to a dark mixture. The mixture was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The aqueous mixture was extracted with EtOAc, washed with aqueous NaHCO3, dried (Na2SO4), filtered and concentrated to afford the titled compound. LCMS calc.=698.22; found=699.30 (M+H)+.

후처리

  1. customwere stirred at 80° C. for 3.5 h
  2. temperaturethen slowly cooled to ambient overnight
  3. customVolatiles were removed under reduced pressure
  4. extractionextracted with EtOAc
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated to a dark mixture
  8. customThe mixture was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  9. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% in 2 min)
  10. customevaporated in vacuo
  11. customto afford an aqueous mixture
  12. extractionThe aqueous mixture was extracted with EtOAc
  13. washwashed with aqueous NaHCO3
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5f5bbf0cabe740419215159f4f25bf06
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07910592B2

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