Dimethylformamide → (S)-2-(4-Chlorophenyl)-N-(2-((R)-1-(cyclopropylamino)-1-oxopropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)propanamide

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(2S)-2-(4-chlorophenyl)propanoic acid	HCID 7023129	—
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	(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-N-cyclopropylpropanamide	HCID 59515716	—
Solvent	Dichloromethane	HCID 6344	—
Product	(S)-2-(4-Chlorophenyl)-N-(2-((R)-1-(cyclopropylamino)-1-oxopropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)propanamide	HCID 59515723	—

Reaction Steps

(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-N-cyclopropylpropanamide (0.2 g, 0.0007 mol), (S)-2-(4-chlorophenyl)propanoic acid (0.16 g, 0.00088 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.33 g, 0.00088 mol), N,N-diisopropylethylamine (0.4 g, 0.003 mol) were stirred in N,N-dimethylformamide (3 mL, 0.04 mol) at room temperature over a weekend. The reaction mixture was diluted with CH2Cl2 (100 mL), washed with NaHCO3 (20 mL×3), dried over Na2SO4, purified via flash chromatography (12 g of silica gel, 0-90% EtOAc/Hexane) and then prep. HPLC gave a white solid. 1H NMR δ (CDCl3) δ: 8.23 (d, J=8.5 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.52-7.39 (m, 5H), 7.22 (d, J=7.6 Hz, 1H), 7.09 (br, 1H), 6.44 (br, 1H), 6.06-6.03 (m, 1H), 5.58 (q, J=7.0 Hz, 1H), 3.83 (q, J=6.7 Hz, 1H), 2.63 (br, 1H), 1.64 (d, J=7.2 Hz, 3H), 1.56 (d, J=5.2 Hz, 3H), 0.78-0.67 (m, 2H), 0.51-0.40 (m, 2H). MS m/z 438.3 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07816371B2
Source dataset	uspto-grants-2010_10
ORD ID	ord-809d467ddc0a4a3fa815a7c178a65fad
Source note	uspto-grants-2010_10