Hydrochloric Acid → 1-[4-(3-Phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamine

HRID 872346Notes

Reaction equation

HRID 872346 reaction equation
C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([CH:26]=[CH2:27])[CH:23]=[CH:22][N:21]4[C:28]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl.O1CCOCC1>CO.C(Cl)Cl>[NH3:7].[C:29]1([C:28]2[N:21]3[CH:22]=[CH:23][C:24]([CH:26]=[CH2:27])=[CH:25][C:20]3=[N:19][C:18]=2[C:15]2[CH:14]=[CH:13][C:12]([C:8]3([NH2:7])[CH2:9][CH2:10][CH2:11]3)=[CH:17][CH:16]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66665226{1-[4-(3-Phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 2

HCID 222AmmoniaHCID 666651691-[4-(3-Phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamineYield 22.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of {1-[4-(3-phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (77 mg, 0.17 mmol) in MeOH (0.7 mL) and CH2Cl2 (1.1 mL) was added a 4 molar solution of HCl in dioxane (0.8 mL, 3.3 mmol, 20 equiv) and the resulting solution was stirred at room temperature for 18 h with monitoring by UPLC-MS. The resulting material was concentrated under reduced pressure. The remaining material (82 mg) was purified using MPLC (Isolute Flash NH2 reverse phase column; 100% CH2Cl2 for 1 min., gradient to 95% CH2Cl2: 5% MeOH over 10 min.; 95% CH2Cl2: 5% MeOH for 5.2 min.) to give partially purified material, which was further purified using preparative HPLC (Waters Autopurification System equipped with pump 254, Sample Manager 2767, CFO, DAD 2996, ELSD 2424 and SQD 3001 using a XBridge C18 5 uM 100×30 mm column; 70% water with 0.2% NH3/30% acetonitrile 1 min., gradient to 30% water with 0.2% NH3/70% acetonitrile over 7 min.) to give 1-[4-(3-phenyl-7-vinyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamine (7 mg, 11%):

Workup

  1. concentrationThe resulting material was concentrated under reduced pressure
  2. customThe remaining material (82 mg) was purified
  3. wait100% CH2Cl2 for 1 min.
  4. waitgradient to 95% CH2Cl2: 5% MeOH over 10 min.
  5. custom95% CH2Cl2: 5% MeOH for 5.2 min.) to give partially purified material, which
  6. customwas further purified
  7. customequipped with pump 254, Sample Manager 2767, CFO, DAD 2996, ELSD 2424 and SQD 3001 using a XBridge C18 5 uM 100×30 mm column

Sources & evidence

ORD record
ord-e586cd1eceed4686be43801a85b416cb
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

Loading…