Iodine → 2-((trans)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)-3-iodoimidazo[1,2-a]pyridine

HRID 2199854Notes

Reaction equation

HRID 2199854 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([C@H:15]3[CH2:17][C@@H:16]3[C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]4[CH:26]=3)[CH:9]=2)[N:3]=1.[I:27]I>C(Cl)Cl>[CH3:1][C:2]1[N:6]=[C:5]([CH3:7])[N:4]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([C@@H:15]3[CH2:17][C@H:16]3[C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]4[C:26]=3[I:27])[CH:9]=2)[N:3]=1

Participants

4

Reactant 2

HCID 807IodineHCID 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

Product 1

HCID 760714242-((trans)-2-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)cyclopropyl)-3-iodoimidazo[1,2-a]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To Example 1 (142 mg, 0.41 mmol) in DCM (4 mL) was added iodine (2.1 g, 8.2 mmol) and the mixture was stirred at room temperature for 1 h. The reaction was quenched with aqueous saturated sodium thiosulfate (2 mL) and methanol (2 mL) and continued to stir at room temperature for 1 h. The reaction mixture was diluted with DCM (15 mL) and the organic layer was washed with saturated aqueous sodium bicarbonate (2×10 mL). The organic layer was then dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (25-70% EtOAc/hexanes) to give Example 8 as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.08 (d, J=6.8 Hz, 1H), 7.60 (s, 1H), 7.50 (d, J=9.0 Hz, 1H), 7.22 (app t, J=7.7 Hz, 1H), 6.89 (app t, J=6.7 Hz, 1H), 2.90 (s, 3H), 2.80-2.71 (m, 2H), 2.69 (s, 3H), 2.39 (s, 3H), 2.00-1.96 (m, 1H), 1.92-1.88 (m, 1H); MS: m/z=472.2 (M+H).

Workup

  1. customThe reaction was quenched with aqueous saturated sodium thiosulfate (2 mL) and methanol (2 mL)
  2. stirringto stir at room temperature for 1 h
  3. additionThe reaction mixture was diluted with DCM (15 mL)
  4. washthe organic layer was washed with saturated aqueous sodium bicarbonate (2×10 mL)
  5. dry with materialThe organic layer was then dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by silica gel chromatography (25-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8bb01951b1b548e2b25dc41d43e9437a
Source dataset
uspto-grants-2016_06
Patent number
US09359348B2

Reaction notes

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