Diisopropylethylamine → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide

HRID 2370861Notes

Reaction equation

HRID 2370861 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@@H:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[NH2:15])[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11].CCCP(=O)=O.[N:29]1[CH:30]=[CH:31][N:32]2[CH:37]=[C:36]([C:38](O)=[O:39])[CH:35]=[CH:34][C:33]=12.CCN(C(C)C)C(C)C>CCOC(C)=O>[F:2][C:3]1[CH:4]=[C:5]([C@@H:14]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[NH:15][C:38]([C:36]2[CH:35]=[CH:34][C:33]3[N:32]([CH:31]=[CH:30][N:29]=3)[CH:37]=2)=[O:39])[CH:6]=[CH:7][C:8]=1[O:9][C:10]([F:13])([F:12])[F:11]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7075376Imidazo(1,2-a)pyridine-6-carboxylic acidHCID 16167369Propylphosphoric anhydrideHCID 86687985(S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride2×

Product 1

HCID 71144375(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)imidazo[1,2-a]pyridine-6-carboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (S)-(3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methanamine hydrochloride (81 mg, 0.238 mmol, Intermediate 6) and EtOAc (3 mL) was added 50% propylphosphonic anhydride in EtOAc (0.28 mL, 0.470 mmol), imidazo[1,2-a]pyridine-6-carboxylic acid (47 mg, 0.290 mmol) and DIPEA (0.12 mL, 0.689 mmol). The solution was stirred at room temperature. After 16 h, the reaction product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (4 g), eluting with 0 to 100% EtOAc in hexane, to provide the title compound as a white solid. 1H NMR (300 MHz, MeOH-d4) δ ppm 9.06-9.16 (m, 1H), 8.44-8.55 (m, 1H), 7.96 (s, 1H), 7.76 (dd, J=9.5, 1.8 Hz, 1H), 7.56-7.71 (m, 3H), 7.42-7.51 (m, 2H), 7.32-7.42 (m, 2H), 6.68-6.76 (m, 1H). MS (ESI pos. ion) m/z: 449.0 (M+H).

Workup

  1. customchromatographed through a Redi-Sep® pre-packed silica gel column (4 g)
  2. washeluting with 0 to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-f14ccb21b59746cc871e663114999e44
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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