2-Aminopyridine → 2-((1S,2S)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)imidazo[1,2-a]pyridine

HRID 2199853Notes

Reaction equation

HRID 2199853 reaction equation
Cl[CH2:2][C:3]([C@H:5]1[CH2:7][C@@H:6]1[C:8]1[CH:13]=[C:12]([N:14]2[C:18]([CH3:19])=[N:17][C:16]([CH3:20])=[N:15]2)[N:11]=[C:10]([CH3:21])[N:9]=1)=O.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)(O)[O-].[Na+]>C(O)C.C(OCC)(=O)C>[CH3:20][C:16]1[N:17]=[C:18]([CH3:19])[N:14]([C:12]2[N:11]=[C:10]([CH3:21])[N:9]=[C:8]([C@H:6]3[CH2:7][C@@H:5]3[C:3]3[N:22]=[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]4[CH:2]=3)[CH:13]=2)[N:15]=1

Participants

6

Reactant 3

HCID 104392-AminopyridineHCID 516892Sodium BicarbonateHCID 901570132-chloro-1-((1S,2S)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)ethanone

Product 1

HCID 1184689102-((1S,2S)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)imidazo[1,2-a]pyridine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-5 (30 mg, 0.10 mmol) and 2-aminopyridine (10 mg, 0.11 mmol) in ethanol (1 mL) was added sodium bicarbonate (16 mg, 0.20 mmol) in a single portion and the reaction was heated at 80° C. After 2 h the mixture cooled to room temperature, diluted with ethyl acetate (5 mL) and washed with saturated aqueous sodium bicarbonate (2×5 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (50-100% EtOAc/hexanes) to give Example 1 as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.03 (dt, J=6.7, 1.2 Hz, 1H), 7.57 (s, 1H), 7.52 (br d, J=9.1 Hz, 1H), 7.45 (s, 1H), 7.13 (ddd, J=9.0, 6.8, 1.2 Hz, 1H), 6.74 (td, J=6.8, 1.1 Hz, 1H), 2.88 (s, 3H), 2.81-2.76 (m, 1H), 2.68-2.62 (m, 1H), 2.65 (s, 3H), 2.39 (s, 3H), 1.93-1.83 (m, 2H); MS: m/z=346.5 (M+H).

Workup

  1. temperatureAfter 2 h the mixture cooled to room temperature
  2. washwashed with saturated aqueous sodium bicarbonate (2×5 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel chromatography (50-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5fc56a2b94f5409a9275e1cb74e782a6
Source dataset
uspto-grants-2016_06
Patent number
US09359348B2

Reaction notes

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