Hydrochloric Acid → 4-(2-(2-Carboxy-ethyl)-3-{6-[3-cyclopropylcarbamoyl-5-(4-methyl-thiophen-3-yl)-phenoxy]-hexyl}-phenoxy)-butyric acid

HRID 1670101노트

반응식

HRID 1670101 반응식
C(OC(CCC1C(OCCCC(OCC)=O)=CC=CC=1CCCCCCOC1C=C([CH:36]=[C:37]([C:39]2[C:43]([CH3:44])=[CH:42][S:41][CH:40]=2)[CH:38]=1)C(O)=O)=O)C.O1C2C=CC(C3C=[C:57]([CH:61]=[C:62]([O:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][C:71]4[CH:76]=[CH:75][CH:74]=[C:73]([O:77][CH2:78][CH2:79][CH2:80][C:81]([O:83]CC)=[O:82])[C:72]=4[CH2:86][CH2:87][C:88]([O:90]CC)=[O:89])C=3)[C:58]([OH:60])=O)=CC=2OCC1.C1CN([P+](Br)([N:104]2[CH2:108][CH2:107][CH2:106]C2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[OH-].[Na+].Cl>C(OCC)(=O)C.C(O)C.ClCCl>[C:88]([CH2:87][CH2:86][C:72]1[C:71]([CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][O:64][C:62]2[CH:38]=[C:37]([C:39]3[C:43]([CH3:44])=[CH:42][S:41][CH:40]=3)[CH:36]=[C:57]([C:58](=[O:60])[NH:104][CH:108]3[CH2:106][CH2:107]3)[CH:61]=2)=[CH:76][CH:75]=[CH:74][C:73]=1[O:77][CH2:78][CH2:79][CH2:80][C:81]([OH:83])=[O:82])([OH:90])=[O:89]

참가 물질

10

반응물 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 673380073-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-5-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-benzoic AcidHCID 673382323-{6-[2-(2-Ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-5-(4-methyl-thiophen-3-yl)-benzoic Acid

생성물 1

HCID 426438864-(2-(2-Carboxy-ethyl)-3-{6-[3-cyclopropylcarbamoyl-5-(4-methyl-thiophen-3-yl)-phenoxy]-hexyl}-phenoxy)-butyric acid

시약·촉매·용매 3

HCID 702Ethanol용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

The acid component, 3-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-5-(4-methyl-thiophen-3-yl)-benzoic acid or 3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-benzoic acid (0.15 mmol), the appropriate amine (1.2 eq.), PyBroP (1.1 eq.), diisopropylethylamine (2 eq.) and dichloromethane (2 mL) were combined together and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate and concentrated to dryness. The material was used without further purification for the next step. The total amount of the product obtained from the previous step was dissolved in ethanol (2 mL) and a 10 M NaOH solution was added (3 eq.). The resulting reaction mixture was stirred at room temperature for 5 h. Then it was neutralized with 3 N HCl and extracted into ethyl acetate. The organic extract was dried over anhydrous sodium sulfate and concentrated to dryness. The crude material was purified on reverse-phase HPLC to afford the title compound.

후처리

  1. washwashed with water and brine
  2. extractionThe organic extract
  3. dry with materialwas dried over anhydrous sodium sulfate
  4. concentrationconcentrated to dryness
  5. customThe material was used without further purification for the next step
  6. customThe total amount of the product obtained from the previous step
  7. customThe resulting reaction mixture
  8. stirringwas stirred at room temperature for 5 h
  9. extractionextracted into ethyl acetate
  10. extractionThe organic extract
  11. dry with materialwas dried over anhydrous sodium sulfate
  12. concentrationconcentrated to dryness
  13. customThe crude material was purified on reverse-phase HPLC

출처 및 근거

ORD 기록
ord-c0d18ecaa46049ed8d32c77400e7010c
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989454B2

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