Diisopropylethylamine → ((S)-1-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester

HRID 604894Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 604894
[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:13](=O)[CH2:14]Br)[CH2:9][CH:10]([CH3:12])[CH3:11])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([NH:41][C:42]([NH2:44])=[S:43])[CH:32]=[CH:33][C:34]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1>>[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:13]1[N:44]=[C:42]([NH:41][C:31]2[CH:32]=[CH:33][C:34]([N:35]3[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]3)=[C:29]([O:28][CH3:27])[CH:30]=2)[S:43][CH:14]=1)[CH2:9][CH:10]([CH3:12])[CH3:11])([CH3:4])([CH3:3])[CH3:2]

Komponenten

4

Edukt 3

HCID 81531DiisopropylethylamineHCID 11034179Tert-butyl N-[(3S)-1-bromo-5-methyl-2-oxohexan-3-YL]carbamateHCID 71650841[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]thiourea

Produkt 1

HCID 86624688((S)-1-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester

Versuchsvorschrift

The title compound was prepared in analogy to example 1 step e) from 102 mg (0.33 mmol) (S)-[1-(2-bromo-acetyl)-3-methyl-butyl]-carbamic acid tert-butyl ester, 42 mg (0.33 mmol) N,N-diisopropyl ethyl amine and 79 mg (0.3 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea. The crude reaction was poured onto water and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated under vacuo. The crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 97 mg (69%) ((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester as a light yellow solid. MS ISP (m/e): 472.3 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.35 (s, 1H), 7.95 (s, 1H), 7.65 (s, 1H), 7.23 (d, 1H), 7.15 (d, 1H), 7.03 (s, 1H), 6.99 (d, 1H), 6.55 (s, 1H), 4.59 (m, 1H), 3.82 (s, 3H), 2.14 (s, 3H), 1.70-1.55 (m, 3H), 1.39 (s, 9H), 0.90 (s, 6H). α589=−43.2; T=20° C.; c=1 g/m100 ml, solvent=MeOH.

Aufarbeitung

  1. customThe crude reaction
  2. additionwas poured onto water
  3. extractionextracted twice with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvent was evaporated under vacuo
  8. customThe crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 97 mg (69%) ((S)-1-{2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-thiazol-4-yl}-3-methyl-butyl)-carbamic acid tert-butyl ester as a light yellow solid
  9. customT=20° C.

Quellen und Nachweise

ORD-Eintrag
ord-84cf3baca01f43ac83e3cb0ed883f8c9
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07910740B2

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