Di-tert-butyl dicarbonate → 9-Methyl-9-azabicyclo(3.3.1)nonan-3-amine

HRID 600652Notes

Reaction equation

HRID 600652 reaction equation
[NH2:1][CH:2]1[CH2:8][C@H:7]2[N:9]([CH3:10])[C@H:4]([CH2:5][CH2:6]2)[CH2:3]1.[C:11](OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH3:11][C:2]1([NH2:1])[CH2:3][CH:4]2[N:9]([CH3:10])[CH:7]([CH2:6][CH2:5]2)[CH2:8]1.[CH3:10][N:9]1[CH:7]2[CH2:8][CH:2]([NH2:1])[CH2:3][CH:4]1[CH2:11][CH2:5][CH2:6]2

Participants

5

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 736442HCID 736442, compoundHCID 21226445Aluminium lithium hydride

Product 2

HCID 144031759-Methyl-9-azabicyclo(3.3.1)nonan-3-amineHCID 67273702HCID 67273702, compound

Procedure

Bicycloamines that can be used in the preparation of the bicyclobase amides are commercially available, can be prepared by known procedures described in the literature, or as described below. For example, 2-Methyl-2-azabicyclo[2.2.2]octan-5-amine was obtained by the reduction of the 2-Boc-2-azabicyclo[2.2.2]octan-5-amine (J. Med. Chem. 1973, 16, 853; Synthesis 1979, 50; WO97/40016). 2-Methyl-2-azabicyclo[2.2.1]heptan-5-amine (Tetrahedron 1998, 54, 8047-8054; J. Med. Chem. 1992, 35, 2184-2191), octahydroindolizin-6-amine (U.S. Pat. No. 4,213,983), 2-azabicyclo[2.2.1]heptan-5-amine (J. Med. Chem. 1990, 33, 1924), 8-azabicyclo[3.2.1]octan-3-amine (WO38680A1; J. Med. Chem., 1993, 36, 3707; J. Med. Chem. 2001, 44, 1815), and 9-azabicyclo[3.3.1]nonan-3-amine (WO38680A1; J. Med. Chem. 1993, 36, 3707; J. Med. Chem. 2001, 44, 1815) were prepared according to literature procedures. 8-Methyl-8-azabicyclo[3.2.1]octan-3-amine was obtained from commercial sources as a variable mixture of endo- and exo-isomers whereas pure exo- and pure endo-isomers were prepared according to the literature (J. Med. Chem. 1998, 41, 988). 3,8-Dimethyl-8-azabicyclo[3.2.1]octan-3-amine was prepared from 3-aminotropane by exposure to di-tert-butyl dicarbonate followed by lithium aluminum hydride reduction. endo-9-Methyl-9-azabicyclo[3.3.1]nonan-3-amine was obtained by the acid hydrolysis of granisetron exo-9-Methyl-9-azabicyclo[3.3.1]nonan-3-amine and a mixture of endo- and exo-9-Methyl-9-azabicyclo[3.3.1]nonan-3-amine may be obtained according to the procedures set forth in European Patent Application No. 0 013 138 A1. 8-Methyl-3,8-diazabicyclo[3.2.1]octane and 3-methyl-3,8-diazabicyclo[3.2.1]octane were prepared from the commercially available 8-Boc protected base by lithium aluminum hydride reduction and reductive alkylation followed by deprotection, respectively.

Workup

  1. customwere prepared

Sources & evidence

ORD record
ord-1ff3f2929be745508af00ffe14ffa0fa
Source dataset
uspto-grants-2011_03
Patent number
US07902217B2

Reaction notes

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