Tetrahydrofuran → 2-{2-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-6-methoxy-phenoxy}-acetamide

HRID 1046926Notes

Reaction equation

HRID 1046926 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:14]=3[O:21][Si](C(C)C)(C(C)C)C(C)C)[N:10]([C:32]([C:34]3[C:39]([F:40])=[CH:38][C:37]([F:41])=[CH:36][C:35]=3[F:42])=[O:33])[N:9]=2)=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.Br[CH2:67][C:68]([NH2:70])=[O:69]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:14]=3[O:21][CH2:67][C:68]([NH2:70])=[O:69])[N:10]([C:32](=[O:33])[C:34]3[C:35]([F:42])=[CH:36][C:37]([F:41])=[CH:38][C:39]=3[F:40])[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 696322-BromoacetamideHCID 2724141Tetrabutylammonium FluorideHCID 67279689[5-(4-Fluoro-phenyl)-2-(3-methoxy-2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone

Product 1

HCID 580258272-{2-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-6-methoxy-phenoxy}-acetamide

Procedure

To [5-(4-fluoro-phenyl)-2-(3-methoxy-2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone (32.3 μmol) is added tetrabutylammonium fluoride in tetrahydrofuran (1 M) (48.5 μmol). The mixture is stirred for an hour and 2-bromo-acetamide (48.5 μmol) is added. The mixture is stirred at room temperature for 12 hours. After evaporation of the solvent the residue is purified by preparative LC/MS (20-100% MeCN/H2O) to give 2-{2-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-6-methoxy-phenoxy}-acetamide: 1H NMR (400 MHz, CDCl3): δ 7.63-7.62 (m, 2H), 7.57 (s, 1H), 7.22-7.12 (m, 3H), 7.02 (dd, J1=8.4 Hz, J2=2 Hz, 2H), 6.9 (bs, 1H), 6.85 (t, J=8.4 Hz, 2H), 6.10 (s, 1H), 4.83 (d, J=15.2 Hz, 1H), 4.68 (d, J=15.2 Hz, 1H), 3.94 (s, 3H).

Workup

  1. stirringThe mixture is stirred at room temperature for 12 hours
  2. customAfter evaporation of the solvent the residue
  3. customis purified by preparative LC/MS (20-100% MeCN/H2O)

Sources & evidence

ORD record
ord-6429ed1877934cdba404c845f58c7b05
Source dataset
uspto-grants-2013_10
Patent number
US08569345B2

Reaction notes

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