Diisopropylethylamine → 2-(((2S,3R)-1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione

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	5-(4-Fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid	HCID 22324125	—
Reactant	2-(((2S,3R)-3-Methylpiperidin-2-yl)methyl)isoindoline-1,3-dione	HCID 117727630	—
Solvent	Dimethylformamide	HCID 6228	—
Product	2-(((2S,3R)-1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione	HCID 117728058	71%

Reaction Steps

To a solution of 2-(((2S,3R)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione (100 mg, 387 μmol) in DMF was added DIPEA (202 μL, 1.16 mmol) followed by 5-(4-fluorophenyl)-2-methylthiazole-4-carboxylic acid (137 mg, 580 μmol) and HATU (176 mg, 465 μmol). The reaction was allowed to stir at rt for 15 h, and was then concentrated in vacuo to remove the DMF. The crude residue was taken up in EtOAc and washed with 1 M HCl, sat aq. NaHCO3, brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (EtOAc/hexanes) to give 2-(((2S,3R)-1-(5-(4-fluorophenyl)-2-methylthiazole-4-carbonyl)-3-methylpiperidin-2-yl)methyl)isoindoline-1,3-dione as a light yellow oil (130 mg, 71%). MS (ESI) 478 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09440982B2
Source dataset	uspto-grants-2016_09
ORD ID	ord-3f6615dd1812482fb8786d663541abf0
Source note	uspto-grants-2016_09