4-Methylmorpholine → N-[(1S,2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamide

HRID 909597Notes

Reaction equation

HRID 909597 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]([CH2:37][OH:38])[C@@H:34]([CH3:36])[OH:35].C1C=CC2N(O)N=NC=2C=1.O.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.[Cl-].[Na+].O>[OH:35][C@H:34]([CH3:36])[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:20])=[O:21])=[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])[CH2:37][OH:38]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 1868194(2S,3R)-2-Amino-1,3-butanediolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666814465-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid

Product 1

HCID 66681687N-[(1S,2R)-2-Hydroxy-1-(hydroxymethyl)propyl]-5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxamideYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.47 g, 3.29 mmol) synthesized in Example (78k), commercially available D-allo-threoninol (0.52 g, 4.94 mmol), HOBT•H2O (0.49 g, 3.62 mmol) and N-methylmorpholine (0.72 mL, 6.58 mmol) were dissolved in N,N-dimethylformamide (10 mL), and WSCI•HCl (0.76 g, 3.95 mmol) was added at room temperature, followed by stirring for 5.5 hours under nitrogen atmosphere. To the reaction solution, saturated brine (40 mL) was added, and extraction was carried out with ethyl acetate (70 mL). After washed with saturated brine, drying was carried out 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: methanol/methylene chloride=0%-6%) to afford the desired compound (1.42 g, 81%) as a white solid.

Workup

  1. extractionextraction
  2. washAfter washed with saturated brine
  3. customdrying
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=0%-6%)

Sources & evidence

ORD record
ord-84a646f0210e4f46babc3b74dade3817
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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