Imidazo(1,2-a)pyridine-3-carboxylic acid → HCID 71280572, compound

HRID 1497942Notes

Reaction equation

HRID 1497942 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.[F:13][C:14]1([F:31])[CH2:16][CH:15]1[C:17]1[O:21][N:20]=[C:19]([C:22]2[C:23]([CH3:30])=[CH:24][C:25]([CH3:29])=[C:26]([CH:28]=2)[NH2:27])[N:18]=1.CCCP(=O)=O>C(OC(=O)C)C.C(=O)(O)[O-].[Na+]>[F:31][C:14]1([F:13])[CH2:16][C@@H:15]1[C:17]1[O:21][N:20]=[C:19]([C:22]2[C:23]([CH3:30])=[CH:24][C:25]([CH3:29])=[C:26]([NH:27][C:10]([C:3]3[N:4]4[CH:9]=[CH:8][CH:7]=[CH:6][C:5]4=[N:1][CH:2]=3)=[O:12])[CH:28]=2)[N:18]=1

Participants

6

Reactant 3

HCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 16167369Propylphosphoric anhydrideHCID 86677533HCID 86677533, compound

Product 1

HCID 71280572HCID 71280572, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
65 °C

Procedure

To a stirring suspension of imidazo[1,2-a]pyridine-3-carboxylic acid (1) (25 mg, 0.154 mmol) and 5-(5-(2,2-difluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2,4-dimethylaniline (150) (41 mg, 0.154 mmol) in ethylacetate (1 mL) was added propylphosphonic anhydride solution 50 wt % in ethyl acetate (184 uL, 0.308 mmol). The reaction was heated at 65° C. overnight. The reaction was cooled to room temperature and diluted with a solution of saturated sodium bicarbonate. The organic was separated and washed with water/brine mixture and dried over anhydrous sodium sulfate. The crude product was purified by silica chromatography and then by a 20×250 mm ChiralPak AD-H column to give (R)—N-(5-(5-(2,2-difluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2,4-dimethylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (F108). 1H NMR (400 MHz, d4-MeOD) δ 10.04 (s, 1H), 9.46-9.44 (m, 1H), 8.57 (s, 1H), 7.95 (s, 1H), 7.79-7.76 (m, 1H), 7.53-7.49 (m, 1H), 7.36 (s, 1H), 7.18-7.15 (m, 1H), 3.74 (m, 1H), 2.55 (s, 3H), 2.47-2.35 (m, 2H), 2.31 (s, 3H). MS m/z 409.14 (M+1)+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe organic was separated
  3. washwashed with 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-d957fbc58f2342e2a5855654fd039cf1
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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