Acrylonitrile → HCID 178461904, compound

HRID 243297Notes

Reaction equation

HRID 243297 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:3][CH2:2]1.[C:28](#[N:31])[CH:29]=[CH2:30]>>[N:27]1[C:19]([NH:18][C@H:16]([C:8]2[N:7]([CH:4]3[CH2:5][CH2:6][N:1]([CH2:30][CH2:29][C:28]#[N:31])[CH2:2][CH2:3]3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH3:17])=[C:20]2[C:24]([NH:23][CH:22]=[N:21]2)=[N:25][CH:26]=1

Participants

3

Reactant 2

HCID 7855AcrylonitrileHCID 178461903HCID 178461903, compound

Product 1

HCID 178461904HCID 178461904, compoundYield 33%

Conditions

Temperature
70 °C

Procedure

A mixture of [(S)-1-(1-piperidin-4-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine 113 (75 mg, 0.207 mmol) and acrylonitrile (75 μL, 1.14 mmol) in IMS (3 mL) was stirred in a sealed tube at 70° C. for 3 h. After cooling to RT, the crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined, concentrated in vacuo and purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM), followed by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-60% 0.1% NH4OH in acetonitrile/water) and finally loaded into an Isolute® SCX-2 which was washed with MeOH and the product eluted with 2M NH3/MeOH. The ammonia fractions were combined and concentrated in vacuo affording 126 as a white solid (28 mg, 33%). LCMS: RT 1.67 min [M+H]+ 416.1. 1H NMR (CDCl3, 400 MHz): δ 8.52 (1H, s), 7.96 (1H, s), 7.80-7.73 (1H, m), 7.65-7.59 (1H, m), 7.26-7.08 (3H, m), 5.29 (1H, bs), 4.69-4.57 (1H, m), 3.09 (1H, bd, J=11.28 Hz), 2.90 (1H, d, J=11.11 Hz), 2.76-2.60 (3H, m), 2.37-2.25 (3H, m), 2.30-2.30 (1H, m), 1.98-1.66 (7H, m)

Workup

  1. temperatureAfter cooling to RT
  2. customthe crude reaction mixture
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  8. customC18 on a 20 min gradient 5-60% 0.1% NH4OH in acetonitrile/water
  9. washwas washed with MeOH
  10. washthe product eluted with 2M NH3/MeOH
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a285e6442bb45629c356a86b8c2bc0a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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