Diisopropylethylamine → HCID 178483543, compound

HRID 2420749Notes

Reaction equation

HRID 2420749 reaction equation
C(N(C(C)C)CC)(C)C.Cl.Cl.[CH3:12][N:13]([CH3:32])[CH2:14][CH2:15][CH2:16][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.[NH2:34][C:35]1[C:36]([C:43]([NH:45][C:46](=[NH:49])SC)=[O:44])=[N:37][C:38]([Cl:42])=[C:39]([NH2:41])[N:40]=1>C(O)C>[CH3:32][N:13]([CH3:12])[CH2:14][CH2:15][CH2:16][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:46]([NH2:49])=[N:45][C:43]([C:36]1[C:35]([NH2:34])=[N:40][C:39]([NH2:41])=[C:38]([Cl:42])[N:37]=1)=[O:44]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 8663423512-Aminododecanoic acid (3-dimethylaminopropyl)amide dihydrochlorideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178483543HCID 178483543, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Diisopropylethylamine (0.23 mL, 1.31 mmol) was added to a suspension of 12-amino-dodecanoic acid (3-dimethylaminopropyl)amide dihydrochloride (5) (0.081 g, 0.22 mmol) in absolute ethanol (5 mL). The mixture became homogeneous. It was stirred at 70° C. (oil bath) for 5 min and then 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.093 g, 0.24 mmol) was added in one portion. The reaction mixture was stirred at this temperature for 3 hours and cooled to room temperature. The solvent was then removed by rotary evaporation, the residue dissolved in small volume of methanol, and this 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 a gradient of 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 (3-dimethylaminopropyl)amide 6 (0.070 g, 63%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 1.25 (m, 14H), 1.50 (m, 6H), 2.01 (t, 2H), 2.11 (s, 6H), 2.20 (t, 2H), 3.02 (m, 2H), 3.12 (t, 2H), 6.80 (br, 3H), 7.75 (m, 1H). m/z (ESI) 512 [C23H42ClN9O2+H]+. mp 82-84° C.

Workup

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

Sources & evidence

ORD record
ord-0c9c911b970a4087ac4ff56699e1f73e
Source dataset
uspto-grants-2011_06
Patent number
US07956059B2

Reaction notes

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