1-Hydroxybenzotriazole → HCID 67058475, compound

https://huagongshe.com/reaction/1919487

Participants

Role	Name	HCID	Charge
Reactant	1-Hydroxybenzotriazole	HCID 75771	—
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	(R)-b-(Boc-amino)-2,5-difluorobenzenebutanoic acid	HCID 11347588	—
Solvent	Dimethylformamide	HCID 6228	—
Product	HCID 67058475	HCID 67058475	64.9%

Reaction Steps

The title compound was prepared from 2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-c]pyrazine (277 mg, 1.45 mmol, from Example 1, Step B), (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoic acid (Intermediate 1, 416 mg, 1.32 mmol), DIPEA (226 mg, 1.58 mol), HOBT (216 mg, 1.98 mol) and HATU (753 mg, 1.98 mol) in DMF (6 mL), using a procedure analogous to that described in Example 1 Step C, except for the purification method. The compound was purified by preparative TLC (silica gel, 20% hexane in ethyl acetate, then 10% methanol in dichloromethane) to give 360 mg of the title compound as a foamy solid. 1H NMR (500 MHz, CDCl3) δ 1.35 (s, 9H), 2.62 (m, 2H), 2.88 (m, 2H) 3.88-4.16 (m, 5H), 4.73 (s, 1H), 4.85 (m, 1H) 5.26-5.39 (m, 1H) 6.90 (bs, 1H), 7.06 (m, 2H), 7.24 (m, 1H). ESI-MS 489 (M+1).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08168637B2
Source dataset	uspto-grants-2012_05
ORD ID	ord-3425487529eb4a3fa64397f361a7d97e
Source note	uspto-grants-2012_05