Dimethylamine → HCID 178489404, compound

HRID 2389038Notes

Reaction equation

HRID 2389038 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:14](=C[CH:16]=2)[N:13](COC(=O)C(C)(C)C)[N:12]=[C:11]3[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])=[CH:4][C:3]=1[C:33](=[O:37])[N:34]([CH3:36])[CH3:35].[C:38](Cl)(Cl)=[O:39].[CH3:42][N:43]([CH3:45])C.C[NH:47]C>ClCCl>[CH3:42][N:43]([CH3:45])[C:38](=[O:39])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:11]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[O:31][CH3:32])=[N:12][NH:13][C:14]3=[N:47][CH:16]=2)=[CH:4][C:3]=1[C:33]([N:34]([CH3:35])[CH3:36])=[O:37]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 1146TrimethylamineHCID 6371PhosgeneHCID 68662452HCID 68662452, compound

Product 1

HCID 178489404HCID 178489404, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2,2-dimethyl-propionic acid 5-(4-amino-3-dimethylcarbamoyl-phenyl)-3-(2-methoxy-phenyl)-indazol-1-ylmethyl ester (0.5 g, 1 mmol) in dichloromethane (10 ml) was stirred at 0° C. for 15 minutes. Then phosgene (673 μl, 1.2 mmol; 20% in toluene) was added and after 1 minute trimethylamine (201 μl, 1.4 mmol), followed by dimethylamine (722 μl, 1.4 mmol; 2 M in THF). The mixture was allowed to stir until the ice melted and then at room temperature for another hour. The crude was worked up by removing solvent and purified on silica chromatography. The resulting product was dissolved in ethanol (6 ml) and 2 M aqueous NaOH (2 ml). The mixture was stirred at room temperature for 4 hours or until no more starting material remained. The solvent was removed under reduced pressure. The crude was neutralized with 1 N HCl and purified on reverse phase HPLC to afford 2-(3,3-dimethyl-ureido)-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide (94 mg, 21% yield). 1H NMR (500 MHz, DMSO-d6) δ 2.91 (s, 6H), 3.01 (s, 6H), 3.84 (s, 3H), 7.09 (m, 1H), 7.22 (d, 1H), 7.46 (m, 1H), 7.65 (d, 1H), 7.69 (s, 1H), 7.77 (d, 1H), 7.96 (d, 1H), 8.32 (s, 1H), 8.64 (s, 1H), 8.85 (s, 1H), 13.80 (s, 1H). MS: m/z 459.2 (M+H+).

Workup

  1. waitat room temperature for another hour
  2. customby removing solvent
  3. custompurified on silica chromatography
  4. dissolutionThe resulting product was dissolved in ethanol (6 ml)
  5. customThe solvent was removed under reduced pressure
  6. custompurified on reverse phase HPLC

Sources & evidence

ORD record
ord-bf73e86b1b7342e6a8058b5dbb9a3589
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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