Dimethylformamide → 6-(3-(tert-butylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 219333Notes

Reaction equation

HRID 219333 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([C:16]4[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=4)[C:19](O)=[O:20])=[CH:12][N:11]3[C:25]=2[C:26](=[O:29])[NH:27][CH3:28])=[CH:4][CH:3]=1.CN(C=O)C.[CH3:35][C:36]([NH2:39])([CH3:38])[CH3:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO>[C:36]([NH:39][C:19]([C:18]1[CH:17]=[C:16]([C:13]2[CH:14]=[CH:15][C:10]3[N:11]([C:25]([C:26]([NH:27][CH3:28])=[O:29])=[C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[N:9]=3)[CH:12]=2)[CH:24]=[CH:23][CH:22]=1)=[O:20])([CH3:38])([CH3:37])[CH3:35]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6385Tert-ButylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592336813-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)imidazo[1,2-a]pyridin-6-yl)benzoic acid

Product 1

HCID 592336576-(3-(tert-butylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamideYield 42%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)imidazo[1,2-a]pyridin-6-yl)benzoic acid (40 mg, 0.10 mmol) was slurried into DMF (0.7 mL) and TEA (0.1 mL). To this slurry was added 2-methylpropan-2-amine (11.27 mg, 0.154 mmol) and then HATU (59 mg, 0.15 mmol) (solution became yellow). The reaction was stirred at rt overnight (complete by LCMS). The reaction was diluted with MeOH (0.7 mL), filtered and purified by prep HPLC (acetonitrile/water, with 10 mM ammonium acetate buffer) to yield 6-(3-(tert-butylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylimidazo[1,2-a]pyridine-3-carboxamide (19.6 mg, 0.042 mmol, 41% yield) as a white solid. 1H NMR (500 MHz, CD3OD) δ ppm 9.25 (br s, 1H), 8.08 (t, J=1.8 Hz, 1H), 7.90 (dd, J=9.2, 1.8 Hz, 1H), 7.88-7.85 (m, 1H), 7.84-7.82 (m, 1H), 7.81-7.78 (m, 2H), 7.77 (br d, J=9.2 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.29 (t, J=8.9 Hz, 2H), 2.69 (s, 3H), 1.52 (s, 9H). LC-MS retention time 1.39 min; m/z 443 (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 mM where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. filtrationfiltered
  2. custompurified by prep HPLC (acetonitrile/water, with 10 mM ammonium acetate buffer)

Sources & evidence

ORD record
ord-3904f1f426e248789ce3dc9a4452d641
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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