PRIMA-1

PRIMA-1 is a mutant p53 reactivator, restores the sensitivity of TP53 mutant-type thyroid cancer cells to the histone methylation inhibitor 3-Deazaneplanocin A.

2,2-bis(hydroxymethyl)-1-azabicyclo[2.2.2]octan-3-one is a member of quinuclidines and a cyclic ketone.

Synthesis of 2, 2-Bis-hydroxymethyl-1-aza-bicyclo [2. 2.2] octan-3-one (2) (in- termediary); The reaction of quinuclidinone hydrochloride (1) (commercially available) (16.9 g, 0.1 mol) with formalin (37percent w/w, 150 mL, 2.0 mol) in the presence of potassium carbonate (15.9 g, 0.11 mol) consumed the starting material after lh at 52 °C. Conversion was followed by LC- MS. The water based reaction mixture was extracted with methylene chloride (4x80 mL) and the combined organic phases were dried over MgS04. The solvent was evaporated off and heptane (500 mL) was added to the residue. After heating for one hour the hot heptane extract was discharged. Benzene (400mL) was added to the residue followed by heating for 8 hours. The resulting mixture was clear filtered from polymer that formed during the heating, and the clear solution was evaporated to dryness. The residue was extracted with boiling heptane (300 mL). After decanting the heptane, boiling benzene (400 mL) was added to the residue. Clear filtra- tion and cooling (to 6°C) followed by isolation by filtration of the solid precipitate yielded 5.1 g of 2, 2-bis-hydroxymethyl-1-aza-bicyclo [2.2. 2] octan-3-one (2) (mp: 136-138 °C). A second crop was isolated from combined mother liquor and material from heptane extraction after precipitation in benzene yielding 2.9 g of the product. In total 37percent yield.

Molecular Weight:185.22
XLogP3:-0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:185.10519334
Monoisotopic Mass:185.10519334
Topological Polar Surface Area:60.8
Heavy Atom Count:13
Complexity:217
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes