Diisopropylethylamine → (2S,3S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester

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	(2S,3S)-1-[(benzyloxy)carbonyl]-3-hydroxypyrrolidine-2-carboxylic acid	HCID 54213972	—
Reactant	4-(2-Amino-thiazol-4-yl)-n-cyclopropyl-benzamide trifluoroacetic acid salt	HCID 86616429	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(2S,3S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester	HCID 57849874	—

Reaction Steps

(2S,3S)-3-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester (41.9 mg, 1.6 mmol) and HATU (66.3 mg, 1.7 mmol) were dissolved in DMF (2 mL). DIEA (55 μL, 0.32 mmol) was then added, and the reaction was stirred at ambient temperature for 15 minutes. Then 4-(2-Amino-thiazol-4-yl)-N-cyclopropyl-benzamide trifluoroacetic acid salt (62.9 mg, 0.17 mmol) was added, and the reaction was stirred at ambient temperature overnight. The reaction was filtered and purified by reverse phase HPLC to give the desired product. Yield 11.8 mg. MS: 507.2 (M+H+); H1 NMR (DMSO-d6): δ(ppm) 0.50-77 (m, 4H), 1.70-2.10 (m, 2H), 4.20-4.40 (m, 1H), 4.86-5.17 (m, 2H), 7.00-7.42 (m, 4H), 7.74-8.01 (m, 5H), 8.40-8.48 (m, 1H), 12.58-12.67 (m, 1H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07595398B2
Source dataset	uspto-grants-2009_09
ORD ID	ord-45d663fe358d4192bd8f752b7fe15eb9
Source note	uspto-grants-2009_09