Triethylamine → (S)-8-(2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione

Participants

Role	Name	HCID	Charge
Reactant	Triethylamine	HCID 8471	—
Reactant	1,3,8-Triazaspiro[4.5]decane-2,4-dione	HCID 120989	—
Reactant	O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate	HCID 2733207	—
Reactant	(S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid	HCID 59732027	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(S)-8-(2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione	HCID 23658011	46%

Reaction Steps

To a solution of (S)-2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (50 mg, 0.133 mmol) in DMF (2.0 mL) were added 1,3,8-triazaspiro[4.5]decane-2,4-dione (34 mg, 0.2 mmol) followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (47 mg, 0.15 mmol) and triethylamine (1.0 mL). After 2 h, the solvent was removed under reduced pressure and the crude product was purified by PrepHPLC to give (S)-8-(2-(4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione (32 mg) in 46% yield. MS (ESI) 527 (M+H); Rf=1.66.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07470680B2
Source dataset	uspto-grants-2008_12
ORD ID	ord-74fdc4e809fb46eea71f96d342cd486d
Source note	uspto-grants-2008_12