Imidazo(1,2-a)pyridine-3-carboxylic acid → HCID 71280764, compound

HRID 1497939Notes

Reaction equation

HRID 1497939 reaction equation
[N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[CH3:13][O:14][C:15]1([C:32]([F:35])([F:34])[F:33])[CH2:18][CH:17]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:25]=[CH:26][C:27]([CH3:31])=[C:28]([CH:30]=3)[NH2:29])[N:20]=2)[CH2:16]1.CCCP(=O)=O>C(OC(=O)C)C.C(=O)(O)[O-].[Na+]>[CH3:13][O:14][C:15]1([C:32]([F:34])([F:35])[F:33])[CH2:16][CH:17]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:25]=[CH:26][C:27]([CH3:31])=[C:28]([NH:29][C:10]([C:3]4[N:4]5[CH:9]=[CH:8][CH:7]=[CH:6][C:5]5=[N:1][CH:2]=4)=[O:12])[CH:30]=3)[N:20]=2)[CH2:18]1

Participants

6

Reactant 3

HCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 16167369Propylphosphoric anhydrideHCID 86677530HCID 86677530, compound

Product 1

HCID 71280764HCID 71280764, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
70 °C

Procedure

A stirring mixture of imidazo[1,2-a]pyridine-3-carboxylic acid (1) (10 mg, 0.064 mmol) and 5-(5-(3-methoxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline (125) (21 mg, 0.064 mmol) in ethylacetate (1 mL) was added propylphosphonic anhydride solution 50 wt. % in ethyl acetate (76 uL, 0.128 mmol). The reaction was heated at 70° C. for 3 hours. The reaction was cooled to room temperature and diluted with a solution of saturated sodium bicarbonate. The organic was separated and washed with 2× water/brine mixture and dried over anhydrous sodium sulfate. The crude product was purified by silica chromatography using DCM:EtOAc:MeOH (1:1:0.1). N-(5-(5-(3-methoxy-3-(trifluoromethyl)cyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (F97). 1H NMR (400 MHz, d6-DMSO) δ 10.06 (s, 1H), 9.47-9.44 (m 1H), 8.59 (s, 1H), 8.08 (d, J=1.6 Hz, 1H), 7.83 (dd, J=1.6, 7.6 Hz, 1H), 7.80-7.78 (m, 1H), 7.55-7.50 (m, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.20-7.16 (m, 1H), 3.76-3.68 (m, 1H), 3.38 (s, 3H), 2.88-2.85 (m, 4H), 2.36 (s, 3H) MS m/z 471.15 (M+1)+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe organic was separated
  3. washwashed with 2× water/brine mixture
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe crude product was purified by silica chromatography

Sources & evidence

ORD record
ord-9bad6df4c0e446f4ad0197f7b3a87a07
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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