Triethylamine → (1-(cyclopropanecarbonyl)piperidin-4-yl)(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methanone

HRID 1923393Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1923393
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[O:19])[N:14]3[CH3:17])=[C:10]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:9]=2)[C:6]2[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=2[N:4]=1)[CH3:2].CCN(CC)CC.[CH:43]1([C:46](Cl)=[O:47])[CH2:45][CH2:44]1>C(Cl)Cl>[CH:43]1([C:46]([N:23]2[CH2:22][CH2:21][CH:20]([C:18]([C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)=[O:19])[CH2:25][CH2:24]2)=[O:47])[CH2:45][CH2:44]1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chlorideHCID 59605539[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-4-ylmethanone

Produkt 1

HCID 59606030(1-(cyclopropanecarbonyl)piperidin-4-yl)(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methanoneAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of [2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-4-ylmethanone (47 mg, 0.10 mmol) and NEt3 (27 μL, 0.20 mmol) in DCM (5 mL) was added cyclopropane carbonyl chloride (10 μL, 0.12 mmol) and the resulting mixture stirred at r.t. for 3 h. The reaction mixture was quenched with H2O and extracted with DCM. The combined organic phases were dried (MgSO4) and concentrated in vacuo and the resulting residue loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 30-70%) affording 864 (13 mg, 25%). LCMS (method I): RT 4.06 min, [M+H]+ 543.3. 1H NMR (CDCl3, 400 MHz): δ 8.07-8.06 (1 H, m), 7.89-7.82 (1 H, m), 7.40-7.30 (2 H, m), 4.70-4.56 (3 H, m), 4.39-4.28 (1 H, m), 4.13 (3 H, s), 3.93-3.90 (6 H, m), 3.52-3.27 (3 H, m), 2.94-2.80 (1 H, m), 2.08-1.97 (2 H, m), 1.97-1.57 (4 H, m), 1.50 (3 H, t, J=7.40 Hz), 1.04-0.98 (2 H, m), 0.79-0.78 (2 H, m)

Aufarbeitung

  1. customThe reaction mixture was quenched with H2O
  2. extractionextracted with DCM
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. washwas washed with MeOH
  6. washthe product eluted with 2M NH3/MeOH
  7. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 30-70%)

Quellen und Nachweise

ORD-Eintrag
ord-b92d6479bbd14db5906516be6e9bf500
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

Notizen zur Reaktion

Wird geladen…