Acetic Acid → 1-{2-[5-Fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-3-azetidinecarboxylic acid

HRID 1942727노트

반응식

HRID 1942727 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=3)=[N:16][N:17]=2)[C:5]([O:11][CH3:12])=[C:6]([CH2:8][CH:9]=O)[CH:7]=1.[NH:32]1[CH2:35][CH:34]([C:36]([OH:38])=[O:37])[CH2:33]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:26])[CH3:27])=[C:20]([C:28]([F:29])([F:30])[F:31])[CH:19]=3)=[N:16][N:17]=2)[C:5]([O:11][CH3:12])=[C:6]([CH2:8][CH2:9][N:32]2[CH2:35][CH:34]([C:36]([OH:38])=[O:37])[CH2:33]2)[CH:7]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 86659002[5-Fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]acetaldehyde

생성물 1

HCID 545795891-{2-[5-Fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-3-azetidinecarboxylic acid수율 42.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

To a solution of [5-fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]acetaldehyde (D35) (90 mg) and 3-azetidinecarboxylic acid (80 mg) in dichloromethane (DCM) (20 mL) stirred at room temperature was added AcOH (0.15 mL). The reaction mixture was stirred at room temperature for 10 min. Then sodium triacetoxyborohydride (84 mg) was added. Stirring continued for overnight. Water was added to quench the reaction, and DCM was removed by evaporation. The mixture was extracted by EA/THF/MeCN for 3 times. The combined organic solution was washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated. The residue was purified by Mass Directed AutoPrep to give 1-{2-[5-fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-3-azetidinecarboxylic acid (E14) (45 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.34 (6H, d), 2.69 (4H, m), 3.17 (3H, m), 3.41 (2H, m), 3.79 (3H, s), 4.94 (1H, m), 7.43 (1H, dd), 7.52 (1H, d), 7.88 (1H, dd), 8.27 (2H, m). δF (DMSO-d6, 376 MHz): −117.2, −61.3. MS (ES): C25H25F4N3O4S requires 539. found 540.1 (M+H+).

후처리

  1. stirringStirring
  2. waitcontinued for overnight
  3. customto quench
  4. customthe reaction, and DCM
  5. customwas removed by evaporation
  6. extractionThe mixture was extracted by EA/THF/MeCN for 3 times
  7. washThe combined organic solution was washed by brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationThe dried solution was filtered
  10. concentrationconcentrated
  11. customThe residue was purified by Mass Directed AutoPrep

출처 및 근거

ORD 기록
ord-73cd12c1498d475bb91366bafd867039
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389508B2

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