Potassium Iodide → 6-[2-[4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl]-ethyl]-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

HRID 580904Notes

Reaction equation

HRID 580904 reaction equation
Cl[CH2:2][CH2:3][C:4]1[C:9](=[O:10])[N:8]2[N:11]=[C:12]([CH3:14])[S:13][C:7]2=[N:6][C:5]=1[CH3:15].[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[CH:21]=[CH:20]2.N1(C2CCN(CCC3C(=O)N4C=CSC4=NC=3C)CC2)C2C(=CC=CC=2)C=C1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].C(=O)([O-])O.[Na+]>CC(C)CC(=O)C.C(OCCO)C>[F:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH:26]1[CH2:31][CH2:30][N:29]([CH2:2][CH2:3][C:4]3[C:9](=[O:10])[N:8]4[N:11]=[C:12]([CH3:14])[S:13][C:7]4=[N:6][C:5]=3[CH3:15])[CH2:28][CH2:27]1)[CH:21]=[CH:20]2

Participants

9

Reactant 6

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 140907595-fluoro-1-(4-piperidinyl)-1H-indoleHCID 155864606-(2-chloroethyl)-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneHCID 700040016-[2-[4-(1H-indol-1-yl)-1-piperidinyl]ethyl]-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one

Product 1

HCID 539566036-[2-[4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl]-ethyl]-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-oneYield 21.8%

Reagents, catalysts & solvents 2

HCID 7909Methyl Isobutyl KetoneSolventHCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture of 6-(2-chloroethyl)-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one (3.6 g), prepared as described in EP-A-0,353,821, 5-fluoro-1-(4-piperidinyl)-1H-indole (3.3 g), prepared according to the procedure described in Synthetic Communications, 18 (3), 265-273 (1988), sodium carbonate (1 g), potassium iodide (catalytic quantity) and sodium hydrogen carbonate (2 g) in 4-methyl-2-pentanone (150 ml) and 2-ethoxyethanol (50 ml) was stirred and refluxed overnight. The mixture was filtered and the filtrate was washed with water. The organic layer was separated, dried, filtered and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 95/5). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from DIPE/CH3CN. The precipitate was filtered off, dried and purified by high-performance liquid chromatography over RP-18 (eluent: (0.5% NH4OAc in H2O)/CH3OH/THF 50/40/10). The pure fractions were collected and the solvent was evaporated, yielding 1.37 g (20%) 6-[2-[4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl]-ethyl]-2,7-dimethyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one (compound 8; mp. 194.1° C.).

Workup

  1. customprepared
  2. customprepared
  3. temperaturerefluxed overnight
  4. filtrationThe mixture was filtered
  5. washthe filtrate was washed with water
  6. customThe organic layer was separated
  7. customdried
  8. filtrationfiltered
  9. customthe solvent evaporated
  10. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /CH3OH 95/5)
  11. customThe pure fractions were collected
  12. customthe solvent was evaporated
  13. customThe residue was crystallized from DIPE/CH3CN
  14. filtrationThe precipitate was filtered off
  15. customdried
  16. custompurified by high-performance liquid chromatography over RP-18 (eluent: (0.5% NH4OAc in H2O)/CH3OH/THF 50/40/10)
  17. customThe pure fractions were collected
  18. customthe solvent was evaporated

Sources & evidence

ORD record
ord-9c99568dc6a74bfa961606b5f72bf554
Source dataset
uspto-grants-1999_07
Patent number
US05919788

Reaction notes

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