Potassium Carbonate → Methyl 4-(4-(dibutylcarbamoyl)-1-(3-hydroxypropyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 529002Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 529002
[CH2:1]([N:5]([CH2:35][CH2:36][CH2:37][CH3:38])[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[C:23]([N:25]2[CH2:34][CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[NH:11][CH:12]=1)=[O:7])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:46][CH2:47][CH2:48][OH:49]>CN(C=O)C.CC(OC)(C)C>[CH2:35]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[C:23]([N:25]2[CH2:34][CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[N:11]([CH2:46][CH2:47][CH2:48][OH:49])[CH:12]=1)=[O:7])[CH2:36][CH2:37][CH3:38]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 178449064HCID 178449064, Verbindung

Produkt 1

HCID 71062328Methyl 4-(4-(dibutylcarbamoyl)-1-(3-hydroxypropyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a stirred solution of methyl 4-(4-(dibutylcarbamoyl)-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (200 mg, 0.38 mmol) in DMF (8 mL) was added K2CO3 (107 mg, 0.77 mmol) and 3-bromopropanol (54 mg, 0.38 mmol). The reaction mixture was heated at 40° C. for 4 h, cooled to room temperature, diluted with MTBE, and quenched with water. The organic layer was separated and the aqueous layer was extracted with MTBE (3×). The combined organic layer was dried over Na2SO4 and concentrated in vacuo to provide crude product. The crude material was purified by flash chromatography (gradient from 10 to 50% EtOAc/hexanes) to provide the title compound (67 mg, 32%). 1H NMR (CDCl3, 1:1 mixture of amide rotamers) δ 8.19-8.15 (m, 1H), 8.04 (dd, J=11.2, 1.6 Hz, 1H), 7.62 (s, 0.5H), 7.55 (s, 0.5H), 7.50-7.46 (m, 1H), 7.25-7.14 (m, 3.5H), 6.94 (d, J=7.2 Hz, 0.5H), 4.84-4.59 (m, 2H), 4.29-4.13 (m, 2H), 3.96 (s, 3H), 3.82-3.70 (m, 2H), 3.50-3.35 (m, 4H), 3.31-2.88 (m, 4H), 1.89-1.87 (m, 2H), 1.55-1.49 (m, 2H), 1.40-1.05 (m, 6H), 0.93-0.88 (m, 3H), 0.74 (t, J=7.2 Hz, 1.5H), 0.65 (t, J=7.2 Hz, 1.5H); MS(ESI+) m/z 575.6 (M+H)+.

Aufarbeitung

  1. temperaturecooled to room temperature
  2. customquenched with water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with MTBE (3×)
  5. dry with materialThe combined organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto provide crude product
  8. customThe crude material was purified by flash chromatography (gradient from 10 to 50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-b871832571d64e3f9d1dcf21787bf13c
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346795B2

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