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Diisopropylethylamine → (2E)-3-[4-({[1-({[3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)phenyl]acrylic acid

HRID 1713946
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1713946
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=O)=[CH:13][CH:14]=3)[N:9]([CH2:19][C:20]([N:22]([CH3:24])[CH3:23])=[O:21])[C:8]=2[C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:63][C:64]1([C:69]([NH:71][C:72]2[CH:77]=[CH:76][C:75](/[CH:78]=[CH:79]/[C:80]([O:82]CC)=[O:81])=[CH:74][CH:73]=2)=[O:70])[CH2:68][CH2:67][CH2:66][CH2:65]1>CN(C=O)C.C1COCC1.CO>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([NH:63][C:64]4([C:69]([NH:71][C:72]5[CH:73]=[CH:74][C:75](/[CH:78]=[CH:79]/[C:80]([OH:82])=[O:81])=[CH:76][CH:77]=5)=[O:70])[CH2:68][CH2:67][CH2:66][CH2:65]4)=[O:18])=[CH:13][CH:14]=3)[N:9]([CH2:19][C:20]([N:22]([CH3:23])[CH3:24])=[O:21])[C:8]=2[C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
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Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114635753-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indole-6-carboxylic acidHCID 58745796Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

Produkt 1

HCID 11621612
(2E)-3-[4-({[1-({[3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)phenyl]acrylic acid
Ausbeute 98 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 21899815MeOH tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution (0.04 M) of 3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indole-6-carboxylic acid (from Step 6) in DMF was treated with DIPEA (3 eq.), HATU (2 eq.) and ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate (from Example 1, Step 7, 1.1 eq.). The solution was stirred at 25° C. for 12 h and then evaporated in vacuo. The residual material was purified by chromatography on silica gel (PE:EtOAc, 8:2, then EtOAc:PE 9:1). The product fractions were evaporated and the material obtained was then dissolved in THF/MeOH (1:1). The resulting solution was treated with LiOH monohydrate (3 eq.) and stirred at RT overnight. The product was isolated by preparative HPLC (stationary phase: Waters Xterra C18 19×150 mm, 5 micron; flow 20 mL/min). After lyophilisation the product was obtained as a colourless amorphous solid (98%).

Aufarbeitung

  1. customevaporated in vacuo
  2. customThe residual material was purified by chromatography on silica gel (PE
  3. customThe product fractions were evaporated
  4. customthe material obtained
  5. stirringstirred at RT overnight
  6. customThe product was isolated by preparative HPLC (stationary phase: Waters Xterra C18 19×150 mm, 5 micron; flow 20 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-880b96217574481d82e86a3f04e1ab36
Quelldatensatz
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07795250B2

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