tert-Butanol → N1-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N3,N3-dipropylisophthalamide

HRID 1783199Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1783199
[NH2:1][C@@H:2]([CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1)[C@H:3]([OH:8])[CH2:4][N:5]=[N+:6]=[N-:7].[CH2:18]([N:21]([CH2:35][CH2:36][CH3:37])[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[C:31]([CH2:33]C)[CH:32]=1)[C:27](O)=[O:28])=[O:23])[CH2:19][CH3:20].C(O)(C)(C)C.C(N(CC)CC)C.C(N=C=NCCCN(C)C)C>ClCCl.C(OCC)(=O)C.CCCCCC.CO.ClCCl>[N:5]([CH2:4][C@@H:3]([OH:8])[C@@H:2]([NH:1][C:27](=[O:28])[C:26]1[CH:30]=[C:31]([CH3:33])[CH:32]=[C:24]([C:22]([N:21]([CH2:18][CH2:19][CH3:20])[CH2:35][CH2:36][CH3:37])=[O:23])[CH:25]=1)[CH2:9][C:10]1[CH:11]=[C:12]([F:17])[CH:13]=[C:14]([F:16])[CH:15]=1)=[N+:6]=[N-:7]

Komponenten

9

Edukt 5

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 225936423-[(Dipropylamino)carbonyl]-5-Ethylbenzoic AcidHCID 57428238(2R,3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-butanol

Produkt 1

HCID 86585849N1-[(1S,2R)-3-azido-1-(3,5-difluorobenzyl)-2-hydroxypropyl]5-methyl-N3,N3-dipropylisophthalamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittelHCID 21226206Ethyl acetate hexaneLösungsmittel

Reaktionsbedingungen

Temperatur
22.5 °C

Versuchsvorschrift

To (2R, 3S)-3-amino-1-azido-4-(3,5-difluorophenyl)-2-buta (XIV, EXAMPLE 166, 0.34 g, 1.4 mmole) in dichloromethane (20 ml) is added N,N-dipropylamidoisophthalic acid (IX, 0.53 g, 2 mmole), t-butyl alcohol (0.27 g, 2 mmole) and triethylamine (0.84 ml, 6 mmole) and ethyl-1-(3-dimethylaminopropyl)carbodiimide (0.58 g, 3 mmole). The mixture is stirred at 20-25 degrees C. for 16 hours. The reaction is monitored by TLC (methanol/dichloromethane, 20/80 +ethyl acetate/hexane, 50/50; Rf=0.76). When the reaction is complete as measured by TLC, the reaction mixture is partitioned between dichloromethane and water, washed with hydrochloric acid (0.5 N), bicarbonate, saline, dried over anhydrous sodium sulfate and the solvent is removed under reduced pressure with heat to produce a concentrate. The concentrate is column chouromatographed on silica gel to give the title compound; MS (MH+)=488.

Aufarbeitung

  1. customthe reaction mixture is partitioned between dichloromethane and water
  2. washwashed with hydrochloric acid (0.5 N), bicarbonate, saline
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent is removed under reduced pressure
  5. temperaturewith heat
  6. customto produce a concentrate

Quellen und Nachweise

ORD-Eintrag
ord-5d15c470fb8b4e158fbe021b237720dc
Quelldatensatz
uspto-grants-2009_03
Patentnummer
US07498436B2

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