Triethylamine → HCID 87242851, compound

HRID 882908Notes

Reaction equation

HRID 882908 reaction equation
C(N(CC)CC)C.[F:8][C:9]([F:14])([F:13])[C:10]([O-:12])=[O:11].[NH2:15][C:16]1[C:17]([C:24]([NH:26][CH2:27][C@@H:28]([N+:32]([CH2:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=2)([CH3:34])[CH3:33])[CH2:29][CH2:30][CH3:31])=[O:25])=[N:18][C:19]([Cl:23])=[C:20]([NH2:22])[N:21]=1.[CH2:45]1[O:47][C@H:46]1[CH2:48][OH:49]>CCO>[F:8][C:9]([F:14])([F:13])[C:10]([O-:12])=[O:11].[NH2:15][C:16]1[C:17]([C:24]([NH:26][CH2:27][C@@H:28]([N+:32]([CH2:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44][CH2:45][C@@H:46]([OH:47])[CH2:48][OH:49])=[CH:40][CH:39]=2)([CH3:34])[CH3:33])[CH2:29][CH2:30][CH3:31])=[O:25])=[N:18][C:19]([Cl:23])=[C:20]([NH2:22])[N:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6973630(-)-Glycidol2×HCID 86656651HCID 86656651, compound

Product 1

HCID 87242851HCID 87242851, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Triethylamine (63.5 μL, 0.46 μmol) is added to a solution of ((S)-1-{[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-methyl}-butyl)-[3-(4-hydroxy-phenyl)-propyl]-dimethyl-ammonium trifluoroacetate (Example 121)(50 mg, 0.091 mmol) in EtOH (5 mL) and the solution is heated to reflux. Once at reflux (S)-glycidol (6.04 μL, 0.091 mmol) is added and the reaction is heated at reflux overnight. Two further portions of (S)-glycidol (2×6.04 μl, 2×0.091 mmol) are added and the reaction is heated at reflux for 24 h. The reaction mixture is concentrated in vacuo and purification by reverse phase chromatography (Isolute™ C18, 0-30% acetonitrile in water with 0.1% TFA) affords the title compound. M+ 509. 1H NMR (400 MHz, DMSO-d6) δ 8.39 (1H, t), 8.20-7.18 (2H, br), 7.24-6.98 (2H, br), 6.99 (2H, d), 6.79 (2H, d), 5.70-3.98 (2H, br), 3.93-3.89 (1H, m), 3.85-3.67 (3H, m), 3.60-3.43 (3H, m), 3.42 (2H, d), 3.39-3.28 (1H, m), 3.04 (3H, s), 3.01 (3H, s), 2.48-2.32 (2H, m), 2.00-1.71 (3H, m), 1.61-1.37 (3H, m), 0.91 (3H, t).

Workup

  1. temperaturethe solution is heated to reflux
  2. additionis added
  3. temperaturethe reaction is heated
  4. temperatureat reflux overnight
  5. temperaturethe reaction is heated
  6. temperatureat reflux for 24 h
  7. concentrationThe reaction mixture is concentrated in vacuo and purification by reverse phase chromatography (Isolute™ C18, 0-30% acetonitrile in water with 0.1% TFA)

Sources & evidence

ORD record
ord-0f35bbf7706b4d0c9e0bcc0493cd27ce
Source dataset
uspto-grants-2012_08
Patent number
US08236808B2

Reaction notes

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