WO2010059773 Aryl methyl benzoquinazolinone M1 receptor positive allosteric modulators

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Scaffold: Benzoquinazolinone

Biological target:

Muscarinic receptor: M1

Activity:

Positive allosteric modulators

Steps Conditions Reactions
a
Toluene, 120oC
b

i. K2CO3, KMNO4, tBuOH/H2O 1/1, 17h

ii). 6N HCl, H2O
Oxidation then hydrolysis
c
HCl, MeOH, 90oC Esterification
d

i). H2, Pd/C, THF, 14h

ii). Br2, dioxane/CCl4 1/1, 0oC, 2h

Amine formation (Nitro reduction)

Bromination
e
NaOH aq, THF, 50oC Saponification
f
BOP, Et3N, CH2Cl2, 15h Amide formation
g N,N-dimethylformamide dimethylacetal, 80oC, 15h Cyclization
h Pd(PPh3)4, THF, 90oC, 7h Negishi cross coupling reaction
Steps Conditions Reactions
a
(Pd(dppf)Cl2.CH2Cl2), THF, 90oC-100oC Negishi cross coupling reaction
b
Cs2CO3, Pd(tBu3)2, THF, 100oC, 20h Suzuki cross coupling reaction
c
CuI, Cs2CO3, DMSO, 130oC, 24h Ullman reaction
d
NaSMe, DMF, 120oC, 15h Nucleophilic substitution
e
mCPBA, CH2Cl2, 0oC S-Oxidation
f
CuI, Cs2CO3, MeOH, microwaves 160oC, 4h Ullman reaction
g MeI, CH3CN, scelled tube, 90oC, 48h  
h TPAP ( Tetrabutylammonium perruthenate: Ley-Griffith reagent) , CH2Cl2, NMO, 30min Oxidation

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