Pyridine → 3-{4-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2263443Notes

Reaction equation

HRID 2263443 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([NH:25][OH:26])=[NH:24])=[C:21]([F:29])[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:47](OC1C=CC=CC=1)=[O:48]>ClCCl>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([F:38])([F:37])[F:39])=[CH:34][CH:35]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]2[NH:24][C:47](=[O:48])[O:26][N:25]=2)=[C:21]([F:29])[CH:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 178513354CID 59594737

Product 1

HCID 1361499453-{4-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of 0.62 g of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-N-hydroxy-benzamidine in 17 mL of dichloromethane at 0° C., under argon, were added 0.23 mL of pyridine and 154 μL of phenyl chloroformate. The reaction mixture was stirred for 10 min at 0° C. followed by 1 h at room temperature. The reaction mixture was concentrated under reduced pressure and the resulting residue was taken up into 10 mL of acetonitrile under argon and 0.165 mL of 1,4-diazabicyclo[5.4.0]undec-7-ene (DBU) was added. The reaction mixture was stirred at room temperature overnight then warmed to 40° C. for 2 h. The reaction mixture was concentrated under reduced pressure. The residue was taken up into dichloromethane and a 1M aqueous solution of NaH2PO4 was added. The aqueous layer was separated and extracted three times with dichloromethane. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 770 mg of crude product as a yellow powder. Purification by column chromatography on silica gel (heptane 1/ethyl acetate 1) gave 150 mg followed by column washing with 100% MeOH gave 320 mg of the title compound. In total, 470 mg of 3-{4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one as white powder was obtained.

Workup

  1. waitfollowed by 1 h at room temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. addition0.165 mL of 1,4-diazabicyclo[5.4.0]undec-7-ene (DBU) was added
  4. stirringThe reaction mixture was stirred at room temperature overnight
  5. temperaturethen warmed to 40° C. for 2 h
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. additiona 1M aqueous solution of NaH2PO4 was added
  8. customThe aqueous layer was separated
  9. extractionextracted three times with dichloromethane
  10. washThe combined organic layers were washed with water
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto give 770 mg of crude product as a yellow powder
  15. customPurification by column chromatography on silica gel (heptane 1/ethyl acetate 1)
  16. customgave 150 mg
  17. washwashing with 100% MeOH

Sources & evidence

ORD record
ord-cf310520df114288aaabe60f7f8ccccc
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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