Diisopropylethylamine → (S)-1-ethyl-3-(4-(6-(3-ethylmorpholino)-7-methyl-7H-purin-2-yl)phenyl)urea

HRID 72177

Reaktionsgleichung

Reaktionsgleichung von HRID 72177
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]([CH3:11])[CH:7]=[N:8]2)=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH2:18][CH3:19])[N:3]=1.Cl.[CH2:21]([C@H:23]1[CH2:28]OC[CH2:25][NH:24]1)[CH3:22].C([N:32]([CH:35]([CH3:37])C)CC)(C)C.[CH2:38](O)[CH3:39].CN(C=[O:45])C>>[CH2:35]([NH:32][C:25]([NH:24][C:23]1[CH:28]=[CH:39][C:38]([C:2]2[N:10]=[C:9]3[C:5]([N:6]([CH3:11])[CH:7]=[N:8]3)=[C:4]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]3[CH2:18][CH3:19])[N:3]=2)=[CH:22][CH:21]=1)=[O:45])[CH3:37]

Komponenten

5

Edukt 4

HCID 81531DiisopropylethylamineHCID 19794673N,N-dimethylformamide ethanolHCID 58222487(S)-4-(2-chloro-7-methyl-7H-purin-6-yl)-3-ethylmorpholineHCID 67094181(3S)-3-Ethylmorpholine--hydrogen chloride (1/1)2×

Produkt 1

HCID 51355343(S)-1-ethyl-3-(4-(6-(3-ethylmorpholino)-7-methyl-7H-purin-2-yl)phenyl)ureaAusbeute 87 %

Versuchsvorschrift

Preparation of (S)-4-(2-chloro-7-methyl-7H-purin-6-yl)-3-ethylmorpholine (e-1) was prepared as described in Example 2 with the modification that (S)-3-ethylmorpholine HCl salt was used in place of morpholine and the 3.5/1 mixture of ethanol/DMF required gentle heating was necessary to effect dissolution of (a-2). Once solubilized, the reaction mixture remained homogeneous upon cooling to room temperature. Diisopropylethylamine and (S)-3-ethylmorpholine HCl were added at room temperature and the reaction stirred for 20 h. Additional heating to 60° C. for 24 h was required for complete conversion to (e-1). The intermediate compound (e-1) was obtained as a tan solid in 87% yield after workup and was taken directly into the next step. 1H NMR (400 MHz, DMSO d6) 8.43 (s, 1H), 4.03 (m, 1H), 3.94 (s, 3H), 3.78 (m, 3H), 3.62 (m, 1H), 3.52 (dd, J=7.3, 18.4 Hz, 2H), 1.79 (m, 2H), 0.79 (t, J=7.4 Hz, 3H). LC/MS-m/z+282.5 (M+H)+.

Aufarbeitung

  1. customwas prepared
  2. temperaturegentle heating
  3. dissolutiondissolution of (a-2)
  4. temperatureAdditional heating to 60° C. for 24 h
  5. customThe intermediate compound (e-1) was obtained as a tan solid in 87% yield after workup

Quellen und Nachweise

ORD-Eintrag
ord-acfc18235c3d42e09b457ece23286f90
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828990B2

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