Piperidine → 2-[(1-Butyrylpiperidin-4-yl)methylamino]-5-chloro-N-(5-chloropyridin-2-yl)benzamide

HRID 1247122Notes

Reaction equation

HRID 1247122 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].C1CCNCC1.CC=C(C)C.[C:37](Cl)(=[O:41])[CH2:38][CH2:39][CH3:40]>C(Cl)(Cl)Cl>[C:37]([N:23]1[CH2:22][CH2:21][CH:20]([CH2:19][NH:18][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:17][C:6]=2[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=2)=[O:8])[CH2:25][CH2:24]1)(=[O:41])[CH2:38][CH2:39][CH3:40]

Participants

6

Reactant 4

HCID 8082PiperidineHCID 8855Butyryl chlorideHCID 105532-Methyl-2-buteneHCID 98861065-chloro-N-(5-chloropyridin-2-yl)-2-[(4-piperidinylmethyl)amino]benzamide

Product 1

HCID 219066632-[(1-Butyrylpiperidin-4-yl)methylamino]-5-chloro-N-(5-chloropyridin-2-yl)benzamideYield 13%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A small sample of 5-chloro-N-(5-chloropyridin-2-yl)-2-[(4-piperidinylmethyl)amino]benzamide from Example 60 (60 mg, 0.16 mmol) was weighed out in a 4 mL sealable vial, followed by (piperidinomethyl)polystyrene (0.12 g, 0.32 mmol). To this was added 10 mL of amylene-stabilized chloroform and butyryl chloride (18.0 μL, 0.17 mmol). The vial was capped and placed in a shaker, where it was kept at room temperature for 24 h, then at 50° C. for 36 h. The crude reaction mixture was then applied to a 2 g SCX column, washed with methanol and eluted with 1 N ammonia in methanol. The yellow fractions were combined and concentrated in vacuo to a dry residue, which was purified by preparative thin layer chromatography. Elution with 9:1 dichloromethane-methanol provided the title compound (9 mg, 13%), isolated in 98% purity by HPLC analysis (Method C: gradient from 50% acetonitrile-50% water with 0.1% trifluoroacetic acid to 90% acetonitrile-10% water with 0.1% trifluoroacetic acid over 10 min; hold 2 min; back to 50% acetonitrile-10% water with 0.1% trifluoroacetic acid over 1 min; hold 2 min; 0.5 ml/min; Waters Symmetry Cl18, 3.5 μM column, 4.6 by 75 mm; 25° C.).

Workup

  1. customThe vial was capped
  2. waitat 50° C. for 36 h
  3. customThe crude reaction mixture
  4. washwashed with methanol
  5. washeluted with 1 N ammonia in methanol
  6. concentrationconcentrated in vacuo to a dry residue, which
  7. customwas purified by preparative thin layer chromatography
  8. washElution with 9:1 dichloromethane-methanol

Sources & evidence

ORD record
ord-841b4ce3fd6445e5bcba2cd83f922ff1
Source dataset
uspto-grants-2006_10
Patent number
US07129245B2

Reaction notes

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