Formic Acid → HCID 178505518, compound

HRID 378945Notes

Reaction equation

HRID 378945 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[CH:14]=[CH:15][S:16][C:11]3=[C:10]([N:17]3[CH2:22][CH2:21][CH:20]([C:23]([NH2:25])=O)[CH2:19][CH2:18]3)[CH:9]=2)=[CH:4][CH:3]=1.[CH:26]([NH:28][NH2:29])=O.C(O)=O>O(Cl)Cl.[P].C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[CH:14]=[CH:15][S:16][C:11]3=[C:10]([N:17]3[CH2:22][CH2:21][CH:20]([C:23]4[N:25]=[CH:26][NH:28][N:29]=4)[CH2:19][CH2:18]3)[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 12229HydrazinecarboxaldehydeHCID 154880041-(5-(4-Fluorophenyl)thieno[3,2-b]pyridin-7-yl)-4-piperidinecarboxamide

Product 1

HCID 178505518HCID 178505518, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 178479709HCID 178479709, compoundSolvent

Procedure

A suspension of 1-(5-(4-fluorophenyl)thieno[3,2-b]pyridin-7-yl)piperidine-4-carboxamide (100 mg, 0.32 mmole) in phosphorus oxochloride (5 mL) is refluxed for about 30 minutes. After the excess phosphorus oxychloride is removed under vacuum, the residue is treated with ethyl acetate (5 mL), and ice-water (10 mL). The mixture is extracted with ethyl acetate (3×10 mL). The combined organic layers are washed with brine, dried over sodium fate, filtered, and concentrated. The residue is dissolved in toluene (5 mL) and then formic hydrazide (100 mg, 1.7 mmole) and formic acid (0.05 mL) are added. The reaction mixture is refluxed for about 16 hours. It is then cooled, diluted with ethyl acetate (15 mL), and washed with water (3×15 mL). The organic layer is dried over sodium sulfate, filtered, and concentrated. The residue is purified by preparative tlc to give 5-(4-fluorophenyl)-7-[4-(1H-1,2,4-triazol-3-yl)-1-piperidinyl]thieno[3,2-b]pyridine (7 mg, 6% yield) as a white solid. This material is dissolved in ethyl acetate (1 mL), saturated with HCl (2 mL), and then concentrated to afford 5-(4-Fluorophenyl)-7-[4-(4H-1,2,4-triazol-3-yl)piperidyl]thioheno[3,2-b]pyridine hydrochloride (compound 2) as greasy oil. Trituration with ether, filtration and drying in vacuo affords the desired product as a solid. m.p. >300° C. (dec).

Workup

  1. temperatureis refluxed for about 30 minutes
  2. customAfter the excess phosphorus oxychloride is removed under vacuum
  3. additionthe residue is treated with ethyl acetate (5 mL), and ice-water (10 mL)
  4. extractionThe mixture is extracted with ethyl acetate (3×10 mL)
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over sodium fate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue is dissolved in toluene (5 mL)
  10. temperatureThe reaction mixture is refluxed for about 16 hours
  11. temperatureIt is then cooled
  12. washwashed with water (3×15 mL)
  13. dry with materialThe organic layer is dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue is purified by preparative tlc

Sources & evidence

ORD record
ord-b5b7547afb9f40f98096bc84a8302899
Source dataset
uspto-grants-2001_10
Patent number
US06297256B1

Reaction notes

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