WO2010049841 7-azaspiro[3.5]nonane-7-carboxamide compounds as modulator of fatty acid amide hydrolase

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Scaffold: 7-azaspiro[3.5]nonane or spiropiperidine

Biological target:

Fatty acid amide hydrolase: FAAH

Activity:

Modulator

Steps	Conditions	Reactions
a	Ph₃PCH₂Br / nBuLi / THF	Alkene synthesis (Wittig reaction)
b	Cl₃CCOCl / Zn-Cu couple / DME	Cyclisation
c	Zn / NH₄Cl / MeOH	Reduction

Steps	Conditions	Reactions
a	MsCl / Et₃N / DCM	Mesyl synthesis
b	NaCN / KI / DMF	Cyanide synthesis
c	NH₂OH / Et₃N / EtOH	Nucleophilic substitution
d	4-(trifluoromethoxy)benzoyl chloride / DIEA / ACN	Cyclisation

Steps	Conditions	Reactions
a	NaBH₄ / MeOH	Hydroxyl synthesis (Ketone reduction)
b	PPh₃ / CBr₄ / THF	Bromination (Appel reaction)
c	Fe(acac)₃ / TMEDA / HMTA / THF	Coupling reaction

Steps	Conditions	Reactions
a	THF	Grignard reaction
b	1. triethylsilane / BF₃-OEt₂ / TFA 2. Boc₂O	Dehydroxylation
c	H₂ / Pd-C / MeOH / AcOEt	Benzyl deprotection
d	Cs₂CO₃ / DMF	Ether formation (nucleophilic substitution)
e	HCl 4N / dioxane	Boc deprotection

Steps	Conditions	Reactions
a	THF	Grignard reaction
b	DAST / DCM	Fluorination

Steps	Conditions	Reactions
a	PS-PPh₃ / DBAD / DCM	Ether synthesis (Mitsunobu reaction)
b	1. TFA / DCM 2. Phenyl (3,4-dimethylisoxazole-5-yl) carbamate / DIEA / ACN	Boc deprotection / Coupling reaction

Steps	Conditions	Reactions
a	LiOH / EtOH	Carboxylic acid synthesis (Cyanide hydrolysis)
b	N,O-dimethylhydroxylamine / HATU / DIEA / DCM	Amide synthesis (HATU coupling)
c	MeMgBr / THF	Weinreb ketone synthesis
d	LDA / TMSCl / NBS / THF	Bromination
e	EtOH	Cyclisation

Steps	Conditions	Reactions
a	NiI₂ / NaHMDS / 2-aminocyclohexanol / isopropanol	Coupling reaction