Sodium Hydroxide → N-{4-Methyl-3-[3-methyl-6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(pentafluoro-lambda6-sulphanyl)-5-(piperazin-1-yl)benzamide

Participants

Role	Name	HCID	Charge
Reactant	Sodium Hydroxide	HCID 14798	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	3-[4-(tert-Butoxycarbonyl)piperazin-1-yl]-5-(pentafluoro-lambda6-sulphanyl)benzoic acid	HCID 89699576	—
Reactant	3-{6-[1-(4-Methoxybenzyl)-1H-pyrazol-4-yl]-3-methyl-1H-imidazo[1,2-b]pyrazol-1-yl}-4-methylaniline	HCID 89699861	—
Solvent	Dimethylformamide	HCID 6228	—
Solvent	Trifluoroacetic acid	HCID 6422	—
Product	N-{4-Methyl-3-[3-methyl-6-(1H-pyrazol-4-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-(pentafluoro-lambda6-sulphanyl)-5-(piperazin-1-yl)benzamide	HCID 136630246	—

Reaction Steps

65 mg (0.16 mmol) of the compound of Example 9A, 68 mg (0.158 mmol) of the compound of Example 16A and 72 mg (0.19 mmol) of HATU were initially charged in 0.9 ml of DMF, 0.033 ml (0.19 mmol) of N,N-diisopropylethylamine were added and the mixture was stirred at RT for 1 h. The reaction was then stirred into 10 ml of 0.1 M aqueous sodium hydroxide solution. After 10 min of further stirring at RT, the precipitate formed was filtered off, washed with water and dried. The intermediate obtained in this manner was dissolved in 0.5 ml of trifluoroacetic acid and stirred at 80° C. for 6 h. The mixture was then concentrated under reduced pressure and the residue was purified by double preparative HPLC (Method 18). This gave 18 mg (19% of theory) of the title compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09394309B2
Source dataset	uspto-grants-2016_07
ORD ID	ord-a891aa5f101f47ecbf3ffe44aa508010
Source note	uspto-grants-2016_07