4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → N-[(1R,2R)-2-Hydroxy-1-methylpropyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

HRID 1964640Notes

Reaction equation

HRID 1964640 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:31])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]([OH:30])=O)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:14]=[N:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=2)[CH:11]=1.[NH2:32][C@H:33]([CH3:37])[C@H:34]([OH:36])[CH3:35].[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO>[OH:36][C@H:34]([CH3:35])[C@H:33]([NH:32][C:28]([C:26]1[NH:27][C:23]([C:8]2[CH:9]=[C:10]([O:12][C:13]3[CH:14]=[N:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=3)[CH:11]=[C:6]([O:5][C@@H:4]([CH3:31])[CH2:3][O:2][CH3:1])[CH:7]=2)=[CH:24][CH:25]=1)=[O:30])[CH3:37]

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 12342906(2R,3R)-3-aminobutan-2-olHCID 666814465-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid

Product 1

HCID 66682238N-[(1R,2R)-2-Hydroxy-1-methylpropyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamideYield 57.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (2.00 g, 4.48 mmol) synthesized in Example (78k) and (2R,3R)-3-aminobutan-2-ol (0.94 g, 8.96 mmol) synthesized in Example (88a) were dissolved in methanol (30 mL), and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n hydrate (2.84 g, 8.96 mmol) was added at room temperature, followed by stirring for 3 days under nitrogen atmosphere. The solvent was distilled off under reduced pressure, water (30 mL) was added, and the solution was separated with ethyl acetate (70 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-90%) to afford the desired compound (1.33 g, 57%) as a white solid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure, water (30 mL)
  2. additionwas added
  3. customthe solution was separated with ethyl acetate (70 mL)
  4. washThe organic layer was washed with saturated brine
  5. dry with materialsubsequently dried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified
  8. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-90%)

Sources & evidence

ORD record
ord-d53ac1c79cd54bb6a3bb0ba3a102ae07
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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