HCID 14734995, compound → 8-Methyl-8-azabicyclo[3.2.1]octan-3-amine

HRID 1724686Notes

Reaction equation

HRID 1724686 reaction equation
[CH3:1][N:2]1[CH2:7][CH:6]2[CH2:8][CH2:9][CH:3]1[CH2:4][CH:5]2[NH2:10].C([N:18]1[CH2:23][CH:22]2[CH2:24][CH2:25][CH:19]1[CH2:20][CH:21]2[NH2:26])(O[C:14](C)(C)[CH3:15])=O.C[N:28]1[CH2:33][CH:32]2[CH2:34][CH:29]1[CH2:30][CH:31]2[NH2:35].C1C2N(CC(N)CC2)CC1>>[CH:3]12[CH2:9][CH:6]([CH:5]([NH2:10])[CH2:4]1)[CH2:7][NH:2]2.[CH:19]12[NH:18][CH:23]([CH2:24][CH2:25]1)[CH2:22][CH:21]([NH2:26])[CH2:20]2.[CH:29]12[NH:28][CH:33]([CH2:14][CH2:15][CH2:34]1)[CH2:32][CH:31]([NH2:35])[CH2:30]2.[CH3:1][N:2]1[CH:3]2[CH2:9][CH2:8][CH:7]1[CH2:6][CH:5]([NH2:10])[CH2:4]2

Participants

8

Reactant 4

HCID 14734995HCID 14734995, compoundHCID 147882832-Methyl-2-azabicyclo[2.2.2]octan-5-amineHCID 202716782-Methyl-2-azabicyclo[2.2.1]heptan-5-amineHCID 67273350tert-butyl 5-amino-2-azabicyclo[2.2.2]octane-2-carboxylate

Product 4

HCID 4083948-Methyl-8-azabicyclo[3.2.1]octan-3-amineHCID 13565856HCID 13565856, compoundHCID 19771533HCID 19771533, compoundHCID 19795924HCID 19795924, 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. customcan be prepared by known procedures

Sources & evidence

ORD record
ord-280ea6c819b346e18b59fc02bffe5b62
Source dataset
uspto-grants-2009_02
Patent number
US07488737B2

Reaction notes

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