Ammonium Chloride → N-[(2R)-2-Hydroxybutyl]-5-(3-{[(2S)-1-methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrole-2-carboxamide

HRID 909614Notes

Reaction equation

HRID 909614 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][Si:13]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH:11]=1.[NH2:32][CH2:33][C@H:34]([OH:37])[CH2:35][CH3:36].CCN=C=NCCCN(C)C.Cl.[Cl-].[NH4+]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[OH:37][C@H:34]([CH2:35][CH3:36])[CH2:33][NH:32][C:28]([C:26]1[NH:27][C:23]([C:8]2[CH:9]=[C:10]([O:12][Si:13]([CH:14]([CH3:15])[CH3:16])([CH:17]([CH3:19])[CH3:18])[CH:20]([CH3:21])[CH3:22])[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 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6999089(2R)-1-aminobutan-2-olHCID 666835375-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxylic acid

Product 1

HCID 66890347N-[(2R)-2-Hydroxybutyl]-5-(3-{[(2S)-1-methoxypropan-2-yl]oxy}-5-[(tripropan-2-ylsilyl)oxy]phenyl)-1H-pyrrole-2-carboxamideYield 85%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxylic acid (1.03 g, 2.30 mmol) synthesized in Example (106c) was dissolved in methylene chloride (20 mL), and (2R)-1-aminobutan-2-ol (0.40 g, 4.49 mmol) synthesized according to a method known to the public (Angew. Chem. Int. Ed. 2007, 46, 2245.), WSC•HCl (1.15 g, 6.00 mmol) and 4-dimethylaminopyridine (280 mg, 2.29 mmol) were added, followed by stirring at room temperature overnight under nitrogen atmosphere. To the reaction solution, a saturated aqueous ammonium chloride solution (30 mL) was added, and extraction was carried out with methylene chloride (30 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%-80%) to afford the desired compound (1.01 g, yield 85%) as a white solid.

Workup

  1. additionwere added
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=60%-80%)

Sources & evidence

ORD record
ord-0eb7813ff8ea44b5b98ac31a5329103e
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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