Diisopropylethylamine → (Z)-[4-[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]-phenylcarbamoyl]-cyclohexyl]-carbamic acid tert-butyl ester

HRID 382036Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 382036
Cl.[N:2]1[C:3](=[O:11])[CH:4]=[C:5]2[C:10]=1[CH:9]=[CH:8][CH:7]=[CH:6]2.[C:12]([O:16][C:17]([NH:19][CH:20]1[CH2:25][CH2:24][CH:23]([C:26]([OH:28])=O)[CH2:22][CH2:21]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].F[P-](F)(F)(F)(F)F.[N:36]1(OC(N(C)C)=[N+](C)C)[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2N=N1.C([N:56]([CH2:60][CH3:61])[CH:57]([CH3:59])[CH3:58])(C)C>CN(C)C=O.Cl>[C:12]([O:16][C:17](=[O:18])[NH:19][CH:20]1[CH2:21][CH2:22][CH:23]([C:26](=[O:28])[NH:36][C:40]2[CH:39]=[CH:44][CH:43]=[C:42]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3/[C:4](=[CH:59]/[C:57]3[NH:56][CH:60]=[CH:61][CH:58]=3)/[C:3](=[O:11])[NH:2]4)[CH:41]=2)[CH2:24][CH2:25]1)([CH3:13])([CH3:14])[CH3:15]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27559964-(((Tert-butoxy)carbonyl)amino)cyclohexane-1-carboxylic acidHCID 194389412H-indol-2-one hydrochloride

Produkt 1

HCID 70201180(Z)-[4-[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]-phenylcarbamoyl]-cyclohexyl]-carbamic acid tert-butyl esterAusbeute 62,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A suspension of (Z)-4-(3-aminophenyl)-1,3-dihydro-3-[(1H-pyrrol-2-yl)methylene)]-2H-indol-2-one hydrochloride (53 mg, 0.157 mmol) (from Example 5 supra) and 4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid (53 mg, 0.204 mmol) (prepared according to K. J. Cutrona et al., Tetrahedron Lett. 37(29):5045-5048 (1996)) in 4 mL of dry N,N-dimethylformamide was treated with O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 77 mg, 0.204 mmol) (Advance ChemTech) and N,N-diisopropylethylamine (88 μL , 0.628 mmol) (Aldrich). The reaction mixture was heated at 60° C. under a nitrogen atmosphere for 15 h. The reaction mixture was then diluted with 20 mL of a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate (3×20 mL). The combined organic extracts were concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 45% ethyl acetate-hexanes elution) provided pure (Z)-[4-[3-[2,3-dihydro-2-oxo-3-[(1H-pyrrol-2-yl)methylene]-1H-indol-4-yl]-phenylcarbamoyl]-cyclohexyl]-carbamic acid tert-butyl ester (51.4 mg, 62%) as a yellow solid.

Aufarbeitung

  1. extractionextracted with ethyl acetate (3×20 mL)
  2. concentrationThe combined organic extracts were concentrated in vacuo
  3. washFlash chromatography (Merck Silica gel 60, 230-400 mesh, 45% ethyl acetate-hexanes elution)

Quellen und Nachweise

ORD-Eintrag
ord-66ead671bf0f4807b39833beeed05077
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06307056B1

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