1-Amino-2-propanol → N-[(2R)-2-Hydroxypropyl]-5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxamide

HRID 1964549Notes

Reaction equation

HRID 1964549 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:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[CH:11]=1.[NH2:32][CH2:33][CH:34]([OH:36])[CH3:35].CCN=C=NCCCN(C)C.Cl.Cl>ClCCl.CN(C)C1C=CN=CC=1>[OH:36][C@H:34]([CH3:35])[CH2:33][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]=[CH: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]

Participants

7

Reactant 4

HCID 41-Amino-2-propanolHCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 666818155-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxylic acid

Product 1

HCID 66680968N-[(2R)-2-Hydroxypropyl]-5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxamideYield 83%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrole-2-carboxylic acid (204 mg, 0.458 mmol) synthesized in Example (18a) was dissolved in dichloromethane (10 mL), and (R)-(+1-amino-2-propanol (72.0 μmL, 0.914 mmol), WSCI.HCl (130 mg, 0.678 mmol) and 4-dimethylaminopyridine (115 mg, 0.941 mmol) were added, followed by stirring at room temperature for 18 hours under nitrogen atmosphere. 1N hydrochloric acid (10 mL) was added, and the solution was separated with dichloromethane (15 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=60%-100%) to afford the desired product (191 mg, yield 83%) as a white solid.

Workup

  1. customthe solution was separated with dichloromethane (15 mL)
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently 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=60%-100%)

Sources & evidence

ORD record
ord-b9af93d6c5fc4cf28cd5e91ca9638c52
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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