Hydrochloric Acid → 5'-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylthio)pyrimidin-5-yl]-2'-fluoro-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

HRID 604688노트

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HRID 604688 반응식
[F:1][C:2]([F:50])([F:49])[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[C:27]([O:44][CH3:45])=[CH:28][C:29]([F:43])=[C:30]([C:32]5[CH:37]=[CH:36][C:35]([C:38]([O:40]C)=[O:39])=[CH:34][C:33]=5[CH3:42])[CH:31]=4)=[CH:24][N:23]=[C:22]([S:46][CH3:47])[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].Cl.CC#N>O1CCOCC1.O>[F:50][C:2]([F:1])([F:49])[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[C:27]([O:44][CH3:45])=[CH:28][C:29]([F:43])=[C:30]([C:32]5[CH:37]=[CH:36][C:35]([C:38]([OH:40])=[O:39])=[CH:34][C:33]=5[CH3:42])[CH:31]=4)=[CH:24][N:23]=[C:22]([S:46][CH3:47])[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 168937Lithium hydroxide, monohydrateHCID 86627638Methyl 5'-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylthio)pyrimidin-5-yl]-2'-fluoro-4'-methoxy-2-methylbiphenyl-4-carboxylate

생성물 1

HCID 249690125'-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylthio)pyrimidin-5-yl]-2'-fluoro-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

Methyl 5′-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylthio)pyrimidin-5-yl]-2′-fluoro-4′-methoxy-2-methylbiphenyl-4-carboxylate (43.8 mg, 0.061 mmol) was dissolved in 1,4-dioxane (1.86 mL) and water (1.16 mL). To the above stirred solution was added lithium hydroxide monohydrate (12.70 mg, 0.303 mmol). The resulting mixture was stirred at room temperature overnight. The reaction crude was then acidified with HCl (1N, aq) to give a milky mixture. This white mixture was dissolved into a clear solution by adding MeCN. The clear solution was purified by 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% for 2 min, 20 mL/min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The resulting aqueous mixture was extracted with EtOAc, washed with aqueous NaHCO3, dried (Na2SO4), filtered and concentrated to afford a light tan glass as the titled compound. LCMS calc.=709.15; found=710.06 (M+H)4. 1H NMR (500 MHz, CD3OD): δ 8.38 (s, 1H), 7.99 (s, 1H), 7.91 (s, 3H), 7.85 (d, J=8 Hz, 1H), 7.31 (d, J=8 Hz, 1H), 7.22 (d, J=8 Hz, 1H), 7.06 (d, J=11.5 Hz, 1H), 5.85 (br s, 1H), 4.75 (br d, J=17 Hz, 1H), 4.35 (t, J=7.25 Hz, 1H), 4.18 (br s, 1H), 3.90 (s, 3H), 2.60 (s, 3H), 2.26 (s, 3H), 0.69 (br d, J=5.5 Hz, 3H).

후처리

  1. customThe reaction crude
  2. customto give a milky mixture
  3. dissolutionThis white mixture was dissolved into a clear solution
  4. customThe clear solution was purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  5. washeluting with MeCN/water+0.1% TFA (10% to 100% organic in 10 min, hold 100% for 2 min, 20 mL/min)
  6. customevaporated in vacuo
  7. customto afford an aqueous mixture
  8. extractionThe resulting aqueous mixture was extracted with EtOAc
  9. washwashed with aqueous NaHCO3
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated

출처 및 근거

ORD 기록
ord-0fc21af12af74d80bf602ae44f910a56
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07910592B2

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