4-Methylmorpholine → Methyl N-{[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]carbonyl}-L-serinate

HRID 909576Notes

Reaction equation

HRID 909576 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](O)=[O:29])=[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.Cl.[CH3:33][O:34][C:35](=[O:40])[C@H:36]([CH2:38][OH:39])[NH2:37].C1C=CC2N(O)N=NC=2C=1.O.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CN(C)C=O>[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]([NH:37][C@H:36]([C:35]([O:34][CH3:33])=[O:40])[CH2:38][OH:39])=[O:29])=[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

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 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 66682685Methyl N-{[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]carbonyl}-L-serinateYield 97.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.60 g, 3.58 mmol) synthesized in Example (78k), L-serine methyl ester hydrochloride (0.61 g, 3.94 mmol), HOBT•H2O (0.53 g, 3.94 mmol) and N-methylmorpholine (0.79 mL, 7.17 mmol) were dissolved in a mixed solvent of methylene chloride (30 mL) and N,N-dimethylformamide (7 mL), and WSCI•HCl (0.82 g, 4.30 mmol) was added at room temperature, followed by stirring for 15 hours under nitrogen atmosphere. The reaction solution was diluted with methylene chloride (100 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and 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%-80%) to afford the desired compound (1.91 g, 97%) as a white solid.

Workup

  1. additionwas added at room temperature
  2. washwashed with 1N hydrochloric acid
  3. dry with materiala saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-80%)

Sources & evidence

ORD record
ord-e88ae502c7204c4587eb29bf285c4b00
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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