Dimethylformamide → HCID 178521260, compound

HRID 1014746Notes

Reaction equation

HRID 1014746 reaction equation
Br[C:2]1[C:3]([NH:9][C:10](=[O:18])[NH:11][CH2:12][C:13]([O:15]CC)=O)=[N:4][CH:5]=[C:6](Br)[N:7]=1.BrC1[C:21]([NH2:27])=[N:22][CH:23]=[C:24](Br)N=1.C(N1[CH:39]=[CH:38]N=C1)(N1C=CN=C1)=O.[CH:40](N(C(C)C)CC)([CH3:42])[CH3:41].Cl.[CH2:50]([O:52][C:53](=O)[CH2:54][NH2:55])[CH3:51].C[N:58](C)C=O>O.O1CCOCC1>[N:24]1[N:58]=[C:21]([C:27]2[CH:39]=[CH:38][C:42]([C:6]3[N:7]=[C:2]4[N:11]([CH2:12][C:13]([N:55]5[CH2:54][CH2:53][O:52][CH2:50][CH2:51]5)=[O:15])[C:10](=[O:18])[NH:9][C:3]4=[N:4][CH:5]=3)=[CH:40][CH:41]=2)[NH:22][CH:23]=1

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 682631,1'-Carbonyldiimidazole2×HCID 81531DiisopropylethylamineHCID 6200042-Amino-3,5-dibromopyrazineHCID 2723640Glycine ethyl ester, hydrochlorideHCID 86626419HCID 86626419, compound

Product 1

HCID 178521260HCID 178521260, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-(3-(3,5-dibromopyrazin-2-yl)ureido)acetate. 3,5-Dibromopyrazin-2-amine (5.00 g, 19.8 mmol), 1,1′-carbonyldiimidazole (3.37 g, 20.8 mmol), diisopropylethylamine (10.3 mL, 7.67 mmol), 1,4-dioxane (7.5 mL), and N,N-dimethylformamide (15 mL) were combined in a 100 mL round-bottom flask with a stirbar, stirred, and heated at 50° C. under a reflux condenser under nitrogen for 4.5 h. More 1,1′-carbonyldiimidazole (0.34 g, 2.08 mmol) was added and the reaction heated at 50° C. for an additional 3.5 h. The resulting reaction mixture was cooled to room temperature and glycine ethyl ester hydrochloride (2.90 g, 20.8 mmol) was added. The resulting reaction mixture was stirred at room temperature for 13 h at which time water was added with vigorous stirring to cause precipitation of solids. The solids were collected by vacuum filtration, washed twice with water and twice with hexane, and dried under vacuum at 45° C. to give the desired product (5.17 g, 68%) as a light orange solid which was contaminated with a small amount of ethyl 2-(3-(5-bromo-3-(1H-imidazol-1-yl)pyrazin-2-yl)ureido)acetate. 1H NMR (400 MHz, DMSO-d6) δ 8.89 (s, 1H) 8.53 (s, 1H) 8.08 (t, J=5.66, 1H) 4.12 (q, J=7.29, 2H) 3.96 (d, J=5.86, 2H) 1.21 (t, J=7.03, 3H); MS (ESI) m/z 383 [M+1]+.

Workup

  1. temperaturethe reaction heated at 50° C. for an additional 3.5 h
  2. customThe resulting reaction mixture
  3. temperaturewas cooled to room temperature
  4. customThe resulting reaction mixture
  5. additionwas added
  6. stirringwith vigorous stirring
  7. customprecipitation of solids
  8. filtrationThe solids were collected by vacuum filtration
  9. washwashed twice with water and twice with hexane
  10. customdried under vacuum at 45° C.

Sources & evidence

ORD record
ord-17271811b8d544e7aa6ced45d2465d62
Source dataset
uspto-grants-2011_07
Patent number
US07981893B2

Reaction notes

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