(3R)-1-Azabicyclo(2.2.2)octan-3-amine → HCID 10131434, compound

HRID 2301882Notes

Reaction equation

HRID 2301882 reaction equation
[NH2:1][C@@H:2]1[CH:7]2[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]2)[CH2:3]1.[CH3:10][C:11]1[N:12]=[C:13]([C:22](OCC)=[O:23])[S:14][C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1.CCO>[N:4]12[CH2:9][CH2:8][CH:7]([CH2:6][CH2:5]1)[C@@H:2]([NH:1][C:22]([C:13]1[S:14][C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:11]([CH3:10])[N:12]=1)=[O:23])[CH2:3]2

Participants

5

Reactant 2

HCID 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 22350452Ethyl 4-methyl-5-phenyl-2-thiazolecarboxylate

Product 1

HCID 10131434HCID 10131434, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The freebase of (R)-3-aminoquinuclidine (1.0 g, 5.02 mmol, 2.26 eq) dissolved in THF (˜5 mL) is added to a solution of the product from Step 89c (0.55 g, 2.22 mmol, 1 eq) in 10 mL EtOH. The mixture is heated under reflux. After 48 h, the mixture is cooled and concentrated in vacuo. The residue is purified by silica gel chromatography using a Biotage Flash 40S column (90:9:1 CHCl3/MeOH/NH4OH) to provide N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-methyl-5-phenyl-1,3-thiazole-2-carboxamide (0.40 g, 55%) as a yellow oil. The p-toluenesulfonic acid salt of the product is made and recrystallized from IPA/ether to give the product as light yellow solid. MS (ESI) for C18H21N3OS m/z 328.2 (M+H)+.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux
  3. temperaturethe mixture is cooled
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel chromatography

Sources & evidence

ORD record
ord-a4175adb7758455187d4267e3b50215d
Source dataset
uspto-grants-2002_12
Patent number
US06500840B2

Reaction notes

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