Acryloyl chloride → HCID 54755903, compound

HRID 530964Notes

Reaction equation

HRID 530964 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]([CH3:20])[CH3:19])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>O1CCCC1>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:18]([CH3:20])[CH3:19])[N:9]=[C:8]([C:4]3[CH:3]=[C:2]([NH:1][C:30](=[O:33])[CH:31]=[CH2:32])[CH:7]=[CH:6][CH:5]=3)[C:16]=12

Participants

5

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 70113938HCID 70113938, compound

Product 1

HCID 54755903HCID 54755903, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tetrahydrofuran (20 mL), compound 22 (219 mg, 0.817 mmol) and diisoproylethylamine (156 μL, 0.895 mmol) was cooled to 0° C. Acryloyl chloride (67 μL, 0.828 mmol) was added and the reaction was allowed to proceed for 1 hour and afterwards concentrated in vacuo. The residue was dissolved in dichloromethane (20 mL) and washed with saturated sodium bicarbonate (20 mL). The aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic layers were dried with MgSO4, filtered and concentrated in vacuo. The product was purified by preparative RP-HPLC and lyophilized (70 mg, 26% yield): 1H NMR (400 MHz, DMSO) δ 10.40 (s, 1H), 8.38 (s, 1H), 8.04 (s, 1H), 7.73 (d, J=8.0, 1H), 7.52 (t, J=7.9, 1H), 7.39 (d, J=7.7, 1H), 6.47 (dd, J=17.0, 10.1, 1H), 6.29 (dd, J=17.0, 2.0, 1H), 5.80 (dd, J=10.1, 2.0, 1H), 5.11 (hept, J=6.6, 1H), 1.51 (d, J=6.7, 6H); 13C NMR (100 MHz, DMSO) δ 163.47, 154.87, 151.90, 150.94, 144.73, 139.53, 132.54, 131.68, 129.88, 127.31, 123.42, 119.96, 119.22, 96.91, 48.80, 21.74; [M+H]+ calculated for C17H18N6O 323.1, found 323.5.

Workup

  1. concentrationafterwards concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  3. washwashed with saturated sodium bicarbonate (20 mL)
  4. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
  5. dry with materialThe combined organic layers were dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe product was purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-11d4c2d4cfe0464bb2971fe0a2e60b9d
Source dataset
uspto-grants-2016_05
Patent number
US09353116B2

Reaction notes

Loading…