Tetrahydrothiopyran-4-one → 5-Chloro-N-(5-chloropyridin-2-yl)-2-[1-(4-thianyl)piperidin-4-ylmethylamino]benzamide

HRID 1883000Notes

Reaction equation

HRID 1883000 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:18][CH2:19][CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[C:6]([CH:17]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)=[O:8].[S:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:18][CH2:19][CH:20]2[CH2:21][CH2:22][N:23]([CH:29]3[CH2:30][CH2:31][S:26][CH2:27][CH2:28]3)[CH2:24][CH2:25]2)=[C:6]([CH:17]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)=[O:8]

Participants

6

Reactant 3

HCID 66173Tetrahydrothiopyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 98861065-chloro-N-(5-chloropyridin-2-yl)-2-[(4-piperidinylmethyl)amino]benzamide

Product 1

HCID 219062685-Chloro-N-(5-chloropyridin-2-yl)-2-[1-(4-thianyl)piperidin-4-ylmethylamino]benzamideYield 84%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 10129899Acetic acid methanolSolvent

Procedure

A solution of 5-chloro-N-(5-chloropyridin-2-yl)-2-(piperidin-4-ylmethylamino)benzamide (0.44 g, 1.2 mmol) in methanol-acetic acid (95:5) (10 mL) was treated with tetrahydrothiopyran-4-one (1.34 g, 11.5 mmol) and sodium cyanoborohydride (4.6 mL of a 1 M solution in tetrahydrofuran). The reaction mixture was stirred at room temperature for 48 h, then heated at 50° C. for an additional 60 h. After cooling to room temperature, the solvent was removed in vacuo; the resulting residue was redissolved in methanol and directly applied to 5×10 g SCX columns, washed with methanol and eluted with dichloromethane-2 N ammonia in methanol (1:1). The product fractions were concentrated in vacuo and the residue was purified via silica gel chromatography. Elution with ethyl acetate followed by ethyl acetate-methanol (9:1) afforded the title compound (0.46 g, 84%) as a yellow solid, which was further purified via trituration in acetonitrile followed by separation of the yellow mother liquor.

Workup

  1. temperatureheated at 50° C. for an additional 60 h
  2. temperatureAfter cooling to room temperature
  3. customthe solvent was removed in vacuo
  4. dissolutionthe resulting residue was redissolved in methanol
  5. washwashed with methanol
  6. washeluted with dichloromethane-2 N ammonia in methanol (1:1)
  7. concentrationThe product fractions were concentrated in vacuo
  8. customthe residue was purified via silica gel chromatography
  9. washElution with ethyl acetate

Sources & evidence

ORD record
ord-cbc309c168454b6e9d4ec88fbe1cffa6
Source dataset
uspto-grants-2004_07
Patent number
US06759414B2

Reaction notes

Loading…