Hydrochloric Acid → 1-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-quinazolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Sodium hydride	HCID 24758	—
Reactant	4-Chloro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinazoline	HCID 59165474	—
Reactant	1-{[2-(Hex-5-enylmethylcarbamoyl)-4-hydroxycyclopentanecarbonyl]amino}-2-vinylcyclopropanecarboxylic acid	HCID 66870274	—
Solvent	Tetrahydrofuran	HCID 8028	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	1-({2-(Hex-5-enyl-methyl-carbamoyl)-4-[2-(4-isopropyl-thiazol-2-yl)-quinazolin-4-yloxy]-cyclopentanecarbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid	HCID 68409678	78%

Reaction Steps

Compound 37 (26 mg, 70 μmol) was dissolved in THF (3 mL, dried with mol. siev.). To this solution was added NaH (60% in oil, 8.2 mg, 210 μmol) and the reaction was incubated for 10 min at ambient temperature. To the reaction mixture was then added compound 39 (17.6 mg, 61 μmol) followed by incubation at ambient temperature for 16 h. To the reaction was then added 0.1 M HCl (aq) and EtOAc, the phases separated and the aqueous phase extracted with another portion of EtOAc. The pooled organic phases were dried (MgSO4), filtered and concentrated in vacuo which gave a crude product which was further purified by flash-chromatography (Silica; DCM:MeOH) to afford the title compound (30 mg, 78%). LC/MS>95%, m/z (ESI+)=632 (MH+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07659245B2
Source dataset	uspto-grants-2010_02
ORD ID	ord-22035a8f7ec3439ab6fd235646400789
Source note	uspto-grants-2010_02