1,1'-Carbonyldiimidazole → HCID 66699756, compound

HRID 388142Notes

Reaction equation

HRID 388142 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:12][CH2:13][CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:9](=[O:11])[NH:10][C:5]2=[N:4][CH:3]=1.BrC1C(N)=NC=C(Br)N=1.C([N:32]([CH:35]([CH3:37])[CH3:36])[CH2:33][CH3:34])(C)C.O1[CH2:43][CH2:42][CH:41](CCN)[CH2:40][CH2:39]1.C(N1C=CN=C1)(N1C=CN=C1)=[O:48]>CS(C)=O.C(OCC)(=O)C.CCCCCC.O>[O:48]=[C:33]1[NH:32][CH:35]([C:36]2[CH:43]=[CH:42][C:41]([C:2]3[N:7]=[C:6]4[N:8]([CH2:12][CH2:13][CH:14]5[CH2:19][CH2:18][O:17][CH2:16][CH2:15]5)[C:9](=[O:11])[NH:10][C:5]4=[N:4][CH:3]=3)=[CH:40][CH:39]=2)[CH2:37][CH2:34]1

Participants

10

Reactant 5

HCID 682631,1'-Carbonyldiimidazole2×HCID 81531DiisopropylethylamineHCID 6200042-Amino-3,5-dibromopyrazineHCID 27731982-(Oxan-4-yl)ethan-1-amineHCID 86626416HCID 86626416, compound

Product 1

HCID 66699756HCID 66699756, compoundYield 44%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
100 °C

Procedure

6-Bromo-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one. 3,5-Dibromopyrazin-2-amine (9.79 g, 38.7 mmol) was dissolved in dimethylsulfoxide (12 mL) with stirring in a 150 mL sealable vessel. Diisopropylethylamine (13.5 mL, 77.4 mmol) was added followed by 2-(tetrahydro-2H-pyran-4-yl)ethanamine (5.00 g, 38.7 mmol). Nitrogen was blown into the vessel to blow out air and the vessel was sealed. The resulting reaction mixture was stirred vigorously and heated at 100° C. for 16 h and then cooled to room temperature. 1,1′-Carbonyldiimidazole (9.41 g, 58.0 mmol) was added and the resulting mixture heated at 70° C. Nitrogen was blown into the vessel to blow out air and the vessel was sealed. The resulting reaction mixture was stirred vigorously and heated at 70° C. for 3 h and then cooled to room temperature. More 1,1′-carbonyldiimidazole (3.14 g, 19.4 mmol) was added and the resulting mixture heated at 70° C. for 3.5 h and then cooled to room temperature. The resulting mixture was diluted with ethyl acetate and poured into a separatory funnel containing water and 50% ethyl acetate in hexane. Solids formed while the separatory funnel was being shaken. The solids were collected by vacuum filtration, washed three times with water and twice with ethyl ether, and dried under vacuum at 45° C. to give the desired product (5.57 g, 44%) as a tan-gray solid. A second batch of solids was collected from the filtrate to give the desired product (1.74 g, 14%) as a tan-gray solid. 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br. s., 1H), 8.03 (s, 1H), 3.82 (t, J=7.03, 4H), 3.23 (td, J=11.62, 1.76, 2H), 1.58-1.70 (m, 4H), 1.42-1.55 (m, 1H), 1.10-1.23 (m, 2H); MS (ESI) m/z 327[M+1]+.

Workup

  1. customthe vessel was sealed
  2. customThe resulting reaction mixture
  3. stirringwas stirred vigorously
  4. temperaturecooled to room temperature
  5. temperaturethe resulting mixture heated at 70° C
  6. customthe vessel was sealed
  7. customThe resulting reaction mixture
  8. stirringwas stirred vigorously
  9. temperatureheated at 70° C. for 3 h
  10. temperaturecooled to room temperature
  11. temperaturethe resulting mixture heated at 70° C. for 3.5 h
  12. temperaturecooled to room temperature
  13. additionpoured into a separatory funnel
  14. customSolids formed while the separatory funnel
  15. stirringwas being shaken
  16. filtrationThe solids were collected by vacuum filtration
  17. washwashed three times with water
  18. dry with materialtwice with ethyl ether, and dried under vacuum at 45° C.

Sources & evidence

ORD record
ord-31fc4e5f01be49bdbe1812a52ae3d057
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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