4-[7-Bromo-2-(3-fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester → [7-Bromo-2-(3-fluoro-2-methyl-benzyl)-3-phenyl-indolizin-1-yl]-piperazin-1-yl-methanone

HRID 1963099Notes

Reaction equation

HRID 1963099 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:34]=3[CH3:40])=[C:18]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:19]3[C:24]=2[CH:23]=[C:22]([Br:25])[CH:21]=[CH:20]3)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[Br:25][C:22]1[CH:21]=[CH:20][N:19]2[C:24]([CH:23]=1)=[C:16]([C:14]([N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)=[O:15])[C:17]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:34]=1[CH3:40])=[C:18]2[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

4

Reactant 1

HCID 677728644-[7-Bromo-2-(3-fluoro-2-methyl-benzyl)-3-phenyl-indolizine-1-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67772516[7-Bromo-2-(3-fluoro-2-methyl-benzyl)-3-phenyl-indolizin-1-yl]-piperazin-1-yl-methanoneYield 25.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of the compound of step 3 (70 mg, 115 μmol) in DCM (4 ml) and TFA (2 ml) was stirred at room temperature for 2 h. The solvents were evaporated and the resulting solid was purified by preparative HPLC. The fractions containing the title compound were combined and lyophilized overnight. The obtained solid was dissolved in a small quantity of MOH, mixed with 0.1 N hydrochloric acid and the mixture lyophilized overnight to give 15 mg of the title compound in the form of [7-bromo-2-(3-fluoro-2-methyl-benzyl)-3-phenyl-indolizin-1-yl]-piperazin-1-yl-methanone hydrochloride with the following characteristics:

Workup

  1. customThe solvents were evaporated
  2. customthe resulting solid was purified by preparative HPLC
  3. additionThe fractions containing the title compound
  4. dissolutionThe obtained solid was dissolved in a small quantity of MOH
  5. additionmixed with 0.1 N hydrochloric acid
  6. waitthe mixture lyophilized overnight

Sources & evidence

ORD record
ord-402495586dd54b60be79cba73cfb5bf8
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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