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

HRID 72177

反応式

HRID 72177 の反応式
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]

参加物

5

反応物 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 回

生成物 1

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

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-acfc18235c3d42e09b457ece23286f90
出典データセット
uspto-grants-2014_09
特許番号
US08828990B2

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