4-Pyridinemethanamine → 1-methyl-5-[(pyridin-4-ylmethyl)-amino]-1H-pyrazole-4-carboxylic acid (4-tert-butyl-phenyl)-amide

HRID 1815204Notes

Reaction equation

HRID 1815204 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:15]=[N:16][N:17]([CH3:20])[C:18]=2Cl)=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:21][CH2:22][C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:15]=[N:16][N:17]([CH3:20])[C:18]=2[NH:21][CH2:22][C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 773174-PyridinemethanamineHCID 86588705N-(4-(Tert-butyl)phenyl)-5-chloro-1-methyl-1H-pyrazole-4-carboxamide

Product 1

HCID 207733791-methyl-5-[(pyridin-4-ylmethyl)-amino]-1H-pyrazole-4-carboxylic acid (4-tert-butyl-phenyl)-amide

Conditions

Temperature
160 °C

Procedure

5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (4-tert-butyl-phenyl)-amide (530 mg, 1.80 mmol) and powered 40% KF/Alumina (1.04 g, effective 6.0 mmol of KF) were combined and treated with IpOH (6 mL). 4-(Aminomethyl)pyridine (3.9 g, 36 mmol) was added. The headspace of the reaction vessel was purged with argon and the reaction vessel was sealed. The reaction was then heated to 160° C. overnight with stirring. The reaction was cooled to RT and filtered under vacuum, washing the collected solid with fresh IpOH. The filtrate was concentrated under reduced pressure and the recovered material was eluted through a 17×2.5 cm column of silica gel with a 14:7:7:1 and 7:7:7:1 Hexane:MtBE:CH2Cl2:MeOH step gradient giving 1-methyl-5-[(pyridin-4-ylmethyl)-amino]-1H-pyrazole-4-carboxylic acid (4-tert-butyl-phenyl)-amide as a white foamy solid. MS: 364 (M+1). Calc'd. for C21H25N5 O—363.46.

Workup

  1. additiontreated with IpOH (6 mL)
  2. customThe headspace of the reaction vessel was purged with argon
  3. customthe reaction vessel was sealed
  4. temperatureThe reaction was cooled to RT
  5. filtrationfiltered under vacuum
  6. washwashing the collected solid with fresh IpOH
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. washthe recovered material was eluted through a 17×2.5 cm column of silica gel with a 14:7:7:1 and 7:7:7:1 Hexane

Sources & evidence

ORD record
ord-8c66a12cdab048489737eee71137c0ed
Source dataset
uspto-grants-2005_04
Patent number
US06878714B2

Reaction notes

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