Trifluoroacetic acid methylene chloride → Methyl 4-(1-(5-chloro-2-(3-(3-(piperazin-1-yl)phenoxy)azetidin-1-yl)nicotinamido)cyclopropyl)benzoate

HRID 72501Notes

Reaction equation

HRID 72501 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:32](=[O:47])[NH:33][C:34]2([C:37]3[CH:42]=[CH:41][C:40]([C:43]([O:45][CH3:46])=[O:44])=[CH:39][CH:38]=3)[CH2:36][CH2:35]2)[C:5]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:14]=[C:15]([N:19]4[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]4)[CH:16]=[CH:17][CH:18]=3)[CH2:9]2)=[N:6][CH:7]=1.FC(F)(F)C(O)=O.ClCCl>ClCCl>[Cl:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([N:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[CH:14]=3)[CH2:9]2)=[C:4]([CH:3]=1)[C:32]([NH:33][C:34]1([C:37]2[CH:42]=[CH:41][C:40]([C:43]([O:45][CH3:46])=[O:44])=[CH:39][CH:38]=2)[CH2:36][CH2:35]1)=[O:47]

Participants

4

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 67958770Tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate

Product 1

HCID 67958605Methyl 4-(1-(5-chloro-2-(3-(3-(piperazin-1-yl)phenoxy)azetidin-1-yl)nicotinamido)cyclopropyl)benzoateYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled solution of tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate (130 mg, 0.196 mmol) in dichloromethane (1 ml) a mixture trifluoroacetic acid/dichloromethane (3 ml/1 ml) was added and the resulting mixture stirred for 15 min. Solvents were evaporated in vacuo to afford a residue that was loaded on SPE-SCX (5 g) cartridge. Ammonia fractions after solvent evaporation afforded the title compound (D156) (105 mg)

Workup

  1. customSolvents were evaporated in vacuo
  2. customto afford a residue that
  3. customAmmonia fractions after solvent evaporation

Sources & evidence

ORD record
ord-5f00722bb44845288b29d3403d13c1dc
Source dataset
uspto-grants-2014_09
Patent number
US08828987B2

Reaction notes

Loading…