Trifluoroacetic acid → N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-(4-(hydroxymethyl)benzyl)-1H-pyrazole-4-carboxamide

HRID 928394Notes

Reaction equation

HRID 928394 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([CH2:15][NH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][CH:26]=3)[CH:23]=2)=[O:18])=[C:10]([CH3:33])[N:9]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[N:9]=[C:10]([CH3:33])[C:11]([CH2:15][NH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([CH2:31][OH:32])=[CH:29][CH:30]=3)[CH:23]=2)=[O:18])=[C:12]([CH3:14])[CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58081225[5-({[1-(4-Hydroxymethyl-benzyl)-1H-pyrazole-4-carbonyl]-amino}-methyl)-4,6-dimethyl-pyridin-2-yl]-carbamic acid tert-butyl ester

Product 1

HCID 56836189N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-(4-(hydroxymethyl)benzyl)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of [5-({[1-(4-Hydroxymethyl-benzyl)-1H-pyrazole-4-carbonyl]-amino}-methyl)-4,6-dimethyl-pyridin-2-yl]-carbamic acid tert-butyl ester (50 mg, 0.11 mmol), 1 mL TFA and 2 mL DCM was stirred of room temperature for 2 h. The mixture was evaporated in vacuo and the residue was purified by preparative HPLC (Macherey-Nagel Nucleosil 250×40 mm, 5 to 100% ACN and 0.1% TFA, flow 40ml/min). The product containing fractions were lyophilised, then dissolved in 1 mL MeOH and the resulting mixture was filtered over a MeOH flushed PL-HCO3 MP-resin column. The column was washed with MeOH, the solvent was removed and the product was dissolved in water/ACN and lyophilised to yield the title compound. 1H-NMR (DMSO-d6, 400 MHz) 8.24 (s, 1H), 7.93 (t, 1H), 7.88 (s, 1H), 7.28-7.30 (s, 2H), 7.21-7.23 (s, 2H), 6.15 (s, 1H), 5.78 (bs, 2H), 5.30 (s, 2H), 5.18 (t, 1H), 4.47 (d, 2H), 4.27 (d, 2H), 2.30 (s, 3H), 2.17 (s, 3H); LCMS (method A) RtA=0.128 min; [M+H]+=366.1.

Workup

  1. customThe mixture was evaporated in vacuo
  2. customthe residue was purified by preparative HPLC (Macherey-Nagel Nucleosil 250×40 mm, 5 to 100% ACN and 0.1% TFA, flow 40ml/min)
  3. additionThe product containing fractions
  4. dissolutiondissolved in 1 mL MeOH
  5. filtrationthe resulting mixture was filtered over a MeOH flushed PL-HCO3 MP-resin column
  6. washThe column was washed with MeOH
  7. customthe solvent was removed
  8. dissolutionthe product was dissolved in water/ACN

Sources & evidence

ORD record
ord-bf695841abbd44a39b23d5d151d116aa
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

Loading…