Dimethylformamide → (S)-N-(2-((R)-2-Amino-2-oxo-1-phenylethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3,4-dichlorophenyl)-propanamide

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
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	(S)-2-(3,4-dichlorophenyl)propanoic acid	HCID 28292773	—
Reactant	(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamide	HCID 59515654	—
Product	(S)-N-(2-((R)-2-Amino-2-oxo-1-phenylethyl)-1-oxo-1,2-dihydroisoquinolin-5-yl)-2-(3,4-dichlorophenyl)-propanamide	HCID 59515817	—

Reaction Steps

A round bottom flask was charged with (R)-2-(5-amino-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamide (120 mg, 0.00041 mol), N,N-dimethylformamide (1.5 mL, 0.019 mol), N,N-diisopropylethylamine (0.1 mL, 0.0008 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.3 g, 0.0008 mol) and (S)-2-(3,4-dichlorophenyl)propanoic acid (0.11 g, 0.00049 mol) and the reaction stirred at room temperature overnight. The solvent was removed and the residue purified by flash chromatography and again by preparative HPLC (reverse phase) to obtain the product as a white solid. MS m/z=495.2 (M+H). 1H NMR (400 MHz; DMSO-d6) δ 9.98 (s, 1H), 8.13-8.11 (d, J=8.37 Hz, 1H), 8.03 (s, 1H), 7.74-7.72 (d, J=7.90 Hz, 1H), 7.64-7.63 (d, J=2.06 Hz, 1H), 7.61-7.59 (d, J=7.94 Hz, 1H), 7.55 (s, 1H), 7.50-7.33 (m, 6H), 7.00-6.98 (d, J=8.02 Hz, 1H), 6.74 (s, 1H), 6.39-6.37 (d, J=8.02 Hz, 1H), 4.02-3.96 (q, J=7.01 Hz, 1H), 1.45-1.43 (d, J=7.55 Hz, 3H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07816371B2
Source dataset	uspto-grants-2010_10
ORD ID	ord-19884ef2b8f445b082baa59036928c15
Source note	uspto-grants-2010_10