Diisopropylethylamine → (s)-2-Chloro-5-fluoro-n-(1-(5-fluoropyridin-2-yl)ethyl)-6-morpholinopyrimidin-4-amine

HRID 573990ノート

反応式

HRID 573990 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([F:14])=[C:4](Cl)[N:3]=1.Cl.[F:17][C:18]1[CH:19]=[CH:20][C:21]([C@@H:24]([NH2:26])[CH3:25])=[N:22][CH:23]=1.CCN(C(C)C)C(C)C>C(O)CCC>[Cl:1][C:2]1[N:3]=[C:4]([NH:26][C@H:24]([C:21]2[CH:20]=[CH:19][C:18]([F:17])=[CH:23][N:22]=2)[CH3:25])[C:5]([F:14])=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 67123789(S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochlorideHCID 866441264-(2,6-Dichloro-5-fluoropyrimidin-4-yl)morpholine

生成物 1

HCID 71612726(s)-2-Chloro-5-fluoro-n-(1-(5-fluoropyridin-2-yl)ethyl)-6-morpholinopyrimidin-4-amine収率 42%

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

反応条件

温度
130 °C

実験手順

A mixture of 4-(2,6-dichloro-5-fluoropyrimidin-4-yl)morpholine (Preparation 11a, 1.18 g, 4.68 mmol), (S)-1-(5-fluoropyridin-2-yl)ethanamine hydrochloride (prepared as described in WO2006/123113, 1.00 g, 4.69 mmol) and N,N′-diisopropylethylamine (3.27 mL, 18.77 mmol) in n-butanol (20 mL) was heated at 130° C. for two days. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine) to give the title compound (0.700 g, 42%) as one major regioisomer. The chemical structures of both regioisomers were confirmed by NMR experiments (gHSQCAD and gHMBCAD).

後処理

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was purified by flash chromatography (0-5% ethyl acetate in hexanes to 5:94:1 ethyl acetate/hexanes/triethylamine)

出典と根拠

ORDレコード
ord-ff3876748bcf4d1296ed001ef327b465
出典データセット
uspto-grants-2015_05
特許番号
US09034311B2

反応ノート

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