Hydrochloric Acid → N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(piperidin-1-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335289Notes

Reaction equation

HRID 335289 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH:40][C:41]=1[F:42])[CH2:5][NH:6][C:7]([C:9]1[CH:10]=[CH:11][C:12]([F:38])=[C:13]([NH:15][C:16]([C:18]2[N:22]3[CH:23]=[CH:24][C:25]([C:27]4[CH:36]=[CH:35][C:30]([C:31](OC)=[O:32])=[C:29]([F:37])[CH:28]=4)=[CH:26][C:21]3=[N:20][CH:19]=2)=[O:17])[CH:14]=1)=[O:8].[N:43]1([CH2:49][CH2:50][NH2:51])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1.Cl>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH:40][C:41]=1[F:42])[CH2:5][NH:6][C:7]([C:9]1[CH:10]=[CH:11][C:12]([F:38])=[C:13]([NH:15][C:16]([C:18]2[N:22]3[CH:23]=[CH:24][C:25]([C:27]4[CH:36]=[CH:35][C:30]([C:31](=[O:32])[NH:51][CH2:50][CH2:49][N:43]5[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]5)=[C:29]([F:37])[CH:28]=4)=[CH:26][C:21]3=[N:20][CH:19]=2)=[O:17])[CH:14]=1)=[O:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 33944N-(2-Aminoethyl)piperidineHCID 71283111Methyl 4-(3-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenylcarbamoyl)imidazo[1,2-a]pyridin-7-yl)-2-fluorobenzoate

Product 1

HCID 71283007N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(piperidin-1-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-(3-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenylcarbamoyl)imidazo[1,2-a]pyridin-7-yl)-2-fluorobenzoate (step 1) (50 mg, 0.087 mmol), 2-piperidin-1-yl-ethylamine (0.260 mmol), and TBD (12.07 mg, 0.087 mmol) in THF (289 μl) were heated to 70° C. for 2 days. The mixture was diluted with water (4 ml) and extracted with DCM using a phase separator. The organic portion was concentrated in vacuo and the residue was dissolved in DMSO. Purification of the crude product was carried out by preparative LC-MS. The resulting fractions were loaded onto a pre-wetted (MeOH) Isolute® SCX-2 cartridge and washed with MeOH. The product was eluted with 7M ammonia in MeOH. The resulting residue was treated with 2M HCl (in EtOH, 1 equiv) and the concentrated in vacuo to afford the title compound as a hydrochloride salt;

Workup

  1. extractionextracted with DCM using a phase separator
  2. concentrationThe organic portion was concentrated in vacuo
  3. dissolutionthe residue was dissolved in DMSO
  4. customPurification of the crude product
  5. washwashed with MeOH
  6. washThe product was eluted with 7M ammonia in MeOH
  7. concentrationthe concentrated in vacuo

Sources & evidence

ORD record
ord-6ab452522fe8480e83a8122fccbd1046
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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