Potassium Carbonate → (3S,5R)-3,5-dimethyl-4-pyridin-2-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 2353139Notes

Reaction equation

HRID 2353139 reaction equation
ClC1N=C(N2CCOCC2)C2SC(CN3C[C@@H](C)N(CC4C=CC=CN=4)[C@@H](C)C3)=CC=2N=1.[CH3:33][C@H:34]1[CH2:39][NH:38][CH2:37][C@@H:36]([CH3:40])[N:35]1[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][N:43]=1.[C:48]([O:52][C:53](N1C[C@H](C)N[C@H](C)C1)=[O:54])([CH3:51])([CH3:50])[CH3:49].Br.BrCC1C=CC=CN=1.C(=O)([O-])[O-].[K+].[K+]>CC#N.C(Cl)Cl>[C:48]([O:52][C:53]([N:38]1[CH2:39][C@@H:34]([CH3:33])[N:35]([CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][N:43]=2)[C@@H:36]([CH3:40])[CH2:37]1)=[O:54])([CH3:51])([CH3:50])[CH3:49]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 10822535tert-butyl (3R,5S)-3,5-dimethylpiperazine-1-carboxylateHCID 57420357HCID 57420357, compoundHCID 57494021HCID 57494021, compound

Product 1

HCID 57494022(3S,5R)-3,5-dimethyl-4-pyridin-2-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Via 2-Chloro-6-((3S,5R)-3,5-dimethyl-4-pyridin-2-ylmethyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, prepared from (2S,6R)-2,6-dimethyl-1-pyridin-2-ylmethyl-piperazine. Amine preparation: (3R,5S)-3,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (845 mg), 2-(bromomethyl)-pyridine hydrobromide (1 g) and potassium carbonate (1.15 g) was heated to reflux in MeCN (10 mL). After heating for 24 h the reaction mixture was diluted with DCM, washed with sodium bicarbonate solution, dried (MgSO4) and the solvent removed in vacuo. The residue was purified by flash chromatography to yield (3S,5R)-3,5-dimethyl-4-pyridin-2-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester (867 mg). Treatment of this compound with HCl in DCM/MeOH yielded the desired amine, which was isolated as the hydrochloride salt.

Workup

  1. temperatureAfter heating for 24 h the reaction mixture
  2. washwashed with sodium bicarbonate solution
  3. dry with materialdried (MgSO4)
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0eca768f485b491e9c4ed0edf44b680c
Source dataset
uspto-grants-2010_07
Patent number
US07750002B2

Reaction notes

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