Diisopropylethylamine → 13-cyclohexyl-6-(1-cyclopropyl-3-isopropyl-4-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-1H-pyrazol-5-yl)-N-(isopropylsulfonyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

Participants

Role	Name	HCID	Charge
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-Methyl-3,8-diazabicyclo(3.2.1)octane--hydrogen chloride (1/2)	HCID 22924350	—
Reactant	5-(13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepin-6-yl)-1-cyclopropyl-3-isopropyl-1H-pyrazole-4-carboxylic acid	HCID 57953737	—
Solvent	Dimethylformamide	HCID 6228	—
Product	13-cyclohexyl-6-(1-cyclopropyl-3-isopropyl-4-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-1H-pyrazol-5-yl)-N-(isopropylsulfonyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamide	HCID 57953796	36%

Reaction Steps

HATU (65.0 mg, 0.171 mmol) was added to a stirring solution of 5-(13-cyclohexyl-10-((isopropylsulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepin-6-yl)-1-cyclopropyl-3-isopropyl-1H-pyrazole-4-carboxylic acid (78 mg, 0.114 mmol), 3-methyl-3,8-diazabicyclo[3.2.1]octane dihydrochloride (45 mg, 0.23 mmol), DIEA (80 μL, 0.456 mmol) in DMF (1 mL) at room temperature. The reaction was allowed to stir for 2 hours. The reaction was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (37 mg, 0.041 mmol, 36% yield) consistent by LCMS and NMR, with sufficient purity by HPLC.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08133884B2
Source dataset	uspto-grants-2012_03
ORD ID	ord-3809e825a4e6464591711a8d529ce579
Source note	uspto-grants-2012_03