1,1'-Carbonyldiimidazole → HCID 86644646, compound

HRID 1401197Notes

Reaction equation

HRID 1401197 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([O:17][C:18]([NH:20][C:21]1([C:24]([OH:26])=O)[CH2:23][CH2:22]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(CC)C(C)C)(C)C.[Br:36][C:37]1[C:38]([NH2:44])=[N:39][CH:40]=[C:41]([Br:43])[N:42]=1>CN(C)C=O.ClCCl.C(OCC)(=O)C>[Br:36][C:37]1[C:38]([NH:44][C:24]([C:21]2([NH:20][C:18](=[O:19])[O:17][C:13]([CH3:14])([CH3:15])[CH3:16])[CH2:22][CH2:23]2)=[O:26])=[N:39][CH:40]=[C:41]([Br:43])[N:42]=1

Participants

8

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 6200042-Amino-3,5-dibromopyrazineHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acid

Product 1

HCID 86644646HCID 86644646, compoundYield 50.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,1′-Carbonyldiimidazole (4.37 g, 27.0 mmol) was added to a stirred solution of 1-(tert-butoxycarbonylamino)cyclopropanecarboxylic acid (4.93 g, 24.50 mmol) in N,N-dimethylformamide (6 mL) and dichloromethane (12 mL) at room temperature. The resulting clear yellow mixture was stirred at room temperature under nitrogen for 4 h. N,N-Diisopropylethylamine (8.54 mL, 49.0 mmol) was added followed by 3,5-dibromopyrazin-2-amine (9.29 g, 36.8 mmol). The resulting mixture was heated at 50° C. under a reflux condenser under nitrogen for 60 h. The resulting mixture was diluted with ethyl acetate and washed with water. The layers were separated and the organic layer washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was taken up in dichloromethane and purified using flash chromatography (Biotage) (5-60% ethyl acetate in hexane). Fractions containing the desired product were combined and concentrated under reduced pressure. The residue was triturated with 15% ethyl acetate in hexane and dried under high vacuum to give the desired product (5.349 g, 12.27 mmol, 50% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.92 (br. s., 1H), 8.76 (s, 1H), 7.70 (br. s., 1H), 1.41 (s, 9H), 1.34-1.40 (m, 2H), 1.02-1.09 (m, 2H); MS (ESI) m/z 437.3 [M+1]+, 459.1 [M+Na]+.

Workup

  1. temperatureThe resulting mixture was heated at 50° C. under a reflux condenser under nitrogen for 60 h
  2. washwashed with water
  3. customThe layers were separated
  4. washthe organic layer washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified
  9. additionFractions containing the desired product
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was triturated with 15% ethyl acetate in hexane
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-cbb9a257a1a5466ab9842d4a37cf8ad7
Source dataset
uspto-grants-2014_12
Patent number
US08907087B2

Reaction notes

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