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

HRID 872326Notes

Reaction equation

HRID 872326 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]([C:26]#[C:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:23]=[CH:22][N:21]4[C:32]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl.O1CCOCC1>CO.C(Cl)Cl>[C:33]1([C:32]2[N:21]3[CH:22]=[CH:23][C:24]([C:26]#[C:27][Si:28]([CH3:31])([CH3:29])[CH3:30])=[CH:25][C:20]3=[N:19][C:18]=2[C:15]2[CH:14]=[CH:13][C:12]([C:8]3([NH2:7])[CH2:11][CH2:10][CH2:9]3)=[CH:17][CH:16]=2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66665439{1-[4-(3-Phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 666650621-[4-(3-Phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamineYield 25.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of {1-[4-(3-phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (84 mg, 0.16 mmol) in MeOH (0.8 mL) and CH2Cl2 (1.3 mL) was added a 4 molar solution of HCl in dioxane (0.8 mL, 3.1 mmol, 20 equiv) and the resulting solution was stirred at room temperature for 18 h with monitoring by UPLC-MS and the resulting solution was concentrated under reduced pressure. The remaining material (84 mg) was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 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.). The resulting partially purified material (48 mg) was triturated with diisopropyl ether to give 1-[4-(3-phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamine (18 mg, 24%). The resulting diisopropyl ether solution was concentrated under reduced pressure. The remaining material was triturated with diisopropyl ether to give 1-[4-(3-phenyl-7-trimethylsilanylethynyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamine (20 mg, 30%, 54% total):

Workup

  1. concentrationthe resulting solution was concentrated under reduced pressure
  2. customThe remaining material (84 mg) was purified
  3. wait100% CH2Cl2 for 1 min.
  4. waitgradient to 95% CH2Cl2: 5% MeOH over 10 min.
  5. wait95% CH2Cl2: 5% MeOH for 5.2 min.)
  6. customThe resulting partially purified material (48 mg) was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-b0d72f1d9084429c9cb5c2a9ffca7c5a
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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