1-Methylcyclopropanecarboxylic acid → (8aS)-7-[(1-Methylcyclopropyl)carbonyl]-2-[(1S,2R)-2-phenylcyclopropyl]tetrahydro imidazo[1,5-a]pyrazine-1,3(2H,5H)-dione

Participants

Role	Name	HCID	Charge
Reactant	1-Methylcyclopropanecarboxylic acid	HCID 81326	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate	HCID 2733207	—
Reactant	(8aS)-N-(2,3-dichlorophenyl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-5,6,8,8a-tetrahydroimidazo[1,5-a]pyrazine-7-carboxamide	HCID 56676510	—
Reactant	(8aS)-2-[(1S,2R)-2-Phenylcyclopropyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione HCl salt	HCID 67300061	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(8aS)-7-[(1-Methylcyclopropyl)carbonyl]-2-[(1S,2R)-2-phenylcyclopropyl]tetrahydro imidazo[1,5-a]pyrazine-1,3(2H,5H)-dione	HCID 67300208	—

Reaction Steps

To a 0.2 M solution of Example 4, D2 (1 eq) in DMF were added 1-methylcyclopropanecarboxylic acid (1.1 eq), DIPEA (2.5 eq) and TBTU (1.5 eq). The reaction mixture was stirred at RT for 12 h. The crude product was purified by preparative RP-HPLC using H2O (0.1% TFA) and MeCN (0.1% TFA) as eluents, affording the title compound. 1H NMR (300 MHz, DMSO-d6, 300K) δ: 7.27-7.09 (5H, m), 4.42-4.32 (1H, m), 4.19 (1H, d, J=9.3 Hz), 4.05-3.95 (1H, m), 3.91-3.82 (1H, m), 2.97-2.81 (3H, m), 2.65-2.57 (1H, m), 2.36-2.26 (1H, m), 1.49-1.40 (1H, m), 1.39-1.30 (1H, m), 1.18 (3H, s), 0.83-0.76 (2H, m), 0.54-0.48 (2H, m). MS (ES) C20H23N3O3 requires: 353, found: 354 (M+H)+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08470823B2
Source dataset	uspto-grants-2013_06
ORD ID	ord-230487b326064c39a6be4746e0b29275
Source note	uspto-grants-2013_06