Diisopropylethylamine → HCID 178512402, compound

HRID 2420757Notes

Reaction equation

HRID 2420757 reaction equation
C(N(C(C)C)CC)(C)C.Cl.Cl.[NH:12]1[CH:16]=[CH:15][N:14]=[C:13]1[NH:17][C:18](=[O:31])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][NH2:30].I.[NH2:33][C:34]1[C:35]([C:42]([NH:44][C:45](=[NH:48])SC)=[O:43])=[N:36][C:37]([Cl:41])=[C:38]([NH2:40])[N:39]=1>C(O)C>[NH:12]1[CH:16]=[CH:15][N:14]=[C:13]1[NH:17][C:18](=[O:31])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:45]([NH2:48])=[N:44][C:42]([C:35]1[C:34]([NH2:33])=[N:39][C:38]([NH2:40])=[C:37]([Cl:41])[N:36]=1)=[O:43]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 67215364HCID 67215364, compoundHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178512402HCID 178512402, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Diisopropylethylamine (0.26 mL, 1.49 mmol) was added to a solution of 12-aminododecanoic acid (1H-imidazol-2-yl)amide dihydrochloride (14) (0.056 mg, 0.16 mmol) in absolute ethanol (5 mL). A white precipitate formed and the reaction was stirred at 70° C. for 10 min, then 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.087 g, 0.22 mmol) was added in one portion. The reaction mixture was stirred at this temperature for 16 hours then cooled to room temperature. The solvent was removed by rotary evaporation and the resulting residue was dissolved in small volume of methanol and the solution passed through an ion exchange resin column (Dowex 550A OH type). The resin was rinsed with methanol and the methanol solution was concentrated in vacuo. The resulting residue was purified by Biotage silica gel column chromatography eluting with 1% to 10% of 9:1 methanol/ammonium hydroxide in dichloromethane to give 12-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]dodecanoic acid (1H-imidazol-2-yl)amide 15 (0.034 g, 44%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 1.25 (m, 14H), 1.50 (m, 4H), 2.29 (t, 2H), 3.09 (m, 2H), 6.61 (m, 4H). m/z (ESI) 493 [C21H33ClN10O2+H]+. mp 102-104° C.

Workup

  1. customA white precipitate formed
  2. stirringThe reaction mixture was stirred at this temperature for 16 hours
  3. temperaturethen cooled to room temperature
  4. customThe solvent was removed by rotary evaporation
  5. dissolutionthe resulting residue was dissolved in small volume of methanol
  6. washThe resin was rinsed with methanol
  7. concentrationthe methanol solution was concentrated in vacuo
  8. customThe resulting residue was purified by Biotage silica gel column chromatography
  9. washeluting with 1% to 10% of 9:1 methanol/ammonium hydroxide in dichloromethane

Sources & evidence

ORD record
ord-a25a4a1f71c94b7f8d657c179bf20549
Source dataset
uspto-grants-2011_06
Patent number
US07956059B2

Reaction notes

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