Diisopropylethylamine → (S)-2-(6-Chloro-1-oxo-5-(2-(4-(trifluoromethyl)phenyl)acetamido)isoquinolin-2(1H)-yl)propanamide

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acid	HCID 118342	—
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-(5-Amino-6-chloro-1-oxoisoquinolin-2(1H)-yl)propanamide	HCID 58973961	—
Product	(S)-2-(6-Chloro-1-oxo-5-(2-(4-(trifluoromethyl)phenyl)acetamido)isoquinolin-2(1H)-yl)propanamide	HCID 25013760	—

Reaction Conditions

Temperature	60 °C

Reaction Steps

A mixture of (S)-2-(5-amino-6-chloro-1-oxoisoquinolin-2(1H)-yl)propanamide (100.0 mg, 0.0003764 mol), 2-(4-(trifluoromethyl)phenyl)acetic acid (115.2 mg, 0.0005646 mol), N,N-diisopropylethylamine (163.9 μL, 0.0009409 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (357.8 mg, 0.0009409 mol) and N,N-dimethylfonnamide (2 mL, 0.02 mol) was stirred at 60° C. for 3 days. The reaction was only about 40% complete. The solvent was removed and the residue purified by preparative HPLC (reverse phase) to obtain the product as light yellow solid. MS m/z=452.1 (M+H). 1H NMR (400 MHz; DMSO-d6) δ10.21 (s, 1H), 8.15 (d, J=8.68 Hz, 1H), 7.74 (d, J=7.76 Hz, 2H), 7.66-7.58 (m, 4H), 7.49 (d, J=7.95 Hz, 1H), 7.25 (s, 1H), 6.43 (d, J=7.50 Hz, 1H), 5.47-5.42 (q, J=7.07 Hz, 1H), 3.90 (s, 2H), 1.53 (d, J=7.39 Hz, 3H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07816371B2
Source dataset	uspto-grants-2010_10
ORD ID	ord-0b863fcad4eb4687ba0ee6d3e301cc06
Source note	uspto-grants-2010_10