Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → 2-(1-Boc-piperidin-4-ylmethylamino)-5-chloro-N-(5-chloropyridin-2-yl)benzamide

HRID 988632Notes

Reaction equation

HRID 988632 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C:17]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:18]=1[C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=1)=[O:20].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[B-][N+](C)(C)C>C1C=CC=CC=1.[OH-].[Na+].O>[C:1]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][NH:16][C:17]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:18]=2[C:19]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=2)=[O:20])[CH2:12][CH2:13]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

8

Reactant 4

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 6327651Borane,N-dimethylmethanamine (1:1)HCID 219064182-Amino-5-chloro-N-(5-chloropyridin-2-yl)benzamide

Product 1

HCID 219066242-(1-Boc-piperidin-4-ylmethylamino)-5-chloro-N-(5-chloropyridin-2-yl)benzamide

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-Boc-piperidine-4-carboxaldehyde (3.5 g, 14 mmol) and 2-amino-5-chloro-N-(5-chloropyridin-2-yl)benzamide (3.9 g, 14 mmol) in benzene (250 mL), a catalytic amount of pyridinium p-toluenesulfonate (0.35 g, 1.4 mmol) was added, followed by 4A molecular sieves. The reaction mixture was heated at reflux for 48 h with azeotropic removal of water. The mixture was subsequently filtered through a pad of diatomaceous earth, washing well with ethyl acetate. The filtrate was concentrated in vacuo to a residue that was taken up in acetic acid (100 mL) and treated with borane-trimethylamine complex (3 g, 42 mmol). The mixture was heated at 70° C. for 24 h; then it was diluted with 2 N NaOH and extracted with dichloromethane The water layer was neutralized with solid sodium bicarbonate, and further extracted with dichloromethane The combined organic extracts were dried with MgSO4, filtered, and concentrated in vacuo to a solid residue (8 g, >100%) which was identified as the desired product and taken on directly to the next step without further purification.

Workup

  1. temperatureThe reaction mixture was heated
  2. filtrationThe mixture was subsequently filtered through a pad of diatomaceous earth
  3. washwashing well with ethyl acetate
  4. concentrationThe filtrate was concentrated in vacuo to a residue that
  5. extractionextracted with dichloromethane The water layer
  6. extractionfurther extracted with dichloromethane The combined organic extracts
  7. dry with materialwere dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a solid residue (8 g, >100%) which
  10. customwithout further purification

Sources & evidence

ORD record
ord-b1ba55f40d0a4e63969551a15c006268
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

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