Ammonium Chloride → HCID 90446569, compound

HRID 1771862Notes

Reaction equation

HRID 1771862 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([N:28]([C:30]4[S:31][CH:32]=[C:33]([C:35]5[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=5)[N:34]=4)[CH3:29])=[C:21]([CH2:23][CH2:24][C:25]([OH:27])=O)[N:22]=3)[CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+:43]>CN(C=O)C.[Cl-].[Na+].O>[NH2:43][C:25](=[O:27])[CH2:24][CH2:23][C:21]1[N:22]=[C:17]2[CH:16]=[CH:15][C:14]([CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9][CH2:10]3)=[CH:19][N:18]2[C:20]=1[N:28]([C:30]1[S:31][CH:32]=[C:33]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=2)[N:34]=1)[CH3:29]

Participants

5

Reactant 2

HCID 25517Ammonium Chloride2×HCID 90420108HCID 90420108, compound

Product 1

HCID 90446569HCID 90446569, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 3-(6-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-a]pyridin-2-yl)propanoic acid (220 mg, 0.38 mmol, 1 eq.) and TEA (211 μL, 1.52 mmol, 4 eq.) in DMF (3 mL) was stirred for 10 min at r.t. Propane phosphonic acid anhydride (226 μL, 0.76 mmol, 2 eq.) followed by ammonium chloride (40.7 mg, 0.76 mmol, 2 eq.) were added and the resulting mixture was stirred at r.t. for 4 days. TEA (211 μL, 1.52 mmol, 4 eq.), propane phosphonic acid anhydride (226 μL, 0.76 mmol, 2 eq.) and ammonium chloride (40.7 mg, 0.76 mmol, 2 eq.) were added and the reaction mixture kept stirring for 2 h. Brine was added (100 mL) and the mixture was extracted with DCM (3×20 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The crude product was purified by chromatography on silica gel (elution with DCM/MeOH 100/0 to 80/20) to give tert-butyl 4-(2-(3-amino-3-oxopropyl)-3-((4-(4-fluorophenyl)thiazol-2-yl)(methyl)amino)imidazo[1,2-a]pyridin-6-yl)piperidine-1-carboxylate (Gen-10-am).

Workup

  1. additionwere added
  2. stirringthe reaction mixture kept stirring for 2 h
  3. extractionthe mixture was extracted with DCM (3×20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography on silica gel (elution with DCM/MeOH 100/0 to 80/20)

Sources & evidence

ORD record
ord-542fe07350e14f68a3b4f4467e01b769
Source dataset
uspto-grants-2016_02
Patent number
US09249141B2

Reaction notes

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