Sodium Bicarbonate → (E)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)-4-(dimethylamino)-2-butenamide

Participants

Role	Name	HCID	Charge
Reactant	Sodium Bicarbonate	HCID 516892	—
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	(2E)-4-(Dimethylamino)-2-butenoic acid hydrochloride	HCID 45358758	—
Reactant	5-(Quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizine-4,8-diamine	HCID 86711283	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(E)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)-4-(dimethylamino)-2-butenamide	HCID 71721577	54.4%

Reaction Steps

HATU (10.3 mg) and 5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizine-4,8-diamine (8.8 mg) obtained in Step 11 of Example 1 were added to a solution of trans-4-dimethylaminocrotonic acid hydrochloride (4.5 mg) in DMF (0.5 ml) at room temperature. After being stirred for 1 hour at the same temperature, the mixture was poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (produced by Wako, NH2 silica-gel 60 F254 plate, developing solvent: chloroform/methanol) to obtain the title compound as a light-yellow solid (6.4 mg).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08889666B2
Source dataset	uspto-grants-2014_11
ORD ID	ord-9d74c321996546108d8d7e0fe803c386
Source note	uspto-grants-2014_11