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1-Hydroxybenzotriazole → Ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate

HRID 1482692
ノート
印刷プレビュー

反応式

HRID 1482692 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:14]([F:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][O:26][CH3:27])=[CH:19][CH:18]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:28]([O:30][C:31](=[O:36])[CH2:32][C:33]([O-])=[O:34])[CH3:29].[K+].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O.CCCCCC.C(OCC)(=O)C>[F:15][C:14]1[C:9]([NH:8][C:4]2[CH:3]=[C:2]([NH:1][C:33](=[O:34])[CH2:32][C:31]([O:30][CH2:28][CH3:29])=[O:36])[CH:7]=[CH:6][CH:5]=2)=[N:10][C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][O:26][CH3:27])=[CH:19][CH:18]=2)=[N:12][CH:13]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3446434Potassium ethyl malonateHCID 59174534N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine

生成物 1

HCID 86724347Ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate
収率 96.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 21226206Ethyl acetate hexane溶媒

実験手順

Into a 25 ml, three neck flask under nitrogen atmosphere, a solution of N4-(3-aminophenyl)-5-fluoro-N2-(4-(2-methoxyethoxy)phenyl)pyrimidine-2,4-diamine (0.15 g) in DMF (5 mL) was charged potassium 3-ethoxy-3-oxopropanoate (0.089 g), EDCI.HCl (0.117 g), HOBt (0.093 g) and TEA (0.164 g). The reaction mixture was stirred for 8 hr at room temperature. Completion of the reaction was monitored by TLC using hexane:ethyl acetate (5:5) as the mobile phase. After completion, the reaction mixture was poured into water. The product was extracted with ethyl acetate and the organic layer was washed with brine. The solvent was removed under reduced pressure at 40° C. The obtained solid was purified by triturating with diethyl ether (2×10 mL) to give 0.19 g of ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate. 1H NMR: DMSO-d6 (400 MHz): 1.182-1.234 (q, 3H, J=6.8), 3.306 (s, 3H), 3.461 (s, 2H), 3.623-3.646 (t, 2H, J=4.8), 4.010-4.033 (t, 2H, J=4.4), 4.090-4.144 (t, 2H, J=7.2), 6.775-6.797 (d, 2H, J=8.8), 7.267-7.283 (d, 2H, J=6.4), 7.511-7.533 (d, 1H, J=8), 7.575-7.591 (d, 1H, J=6.4), 7.817 (s, 1H), 8.058-8.066 (d, 1H, J=3.2), 8.963 (s, 1H), 9.375 (s, 1H), 10.162 (s, 1H).

後処理

  1. extractionThe product was extracted with ethyl acetate
  2. washthe organic layer was washed with brine
  3. customThe solvent was removed under reduced pressure at 40° C
  4. customThe obtained solid was purified
  5. customby triturating with diethyl ether (2×10 mL)

出典と根拠

ORDレコード
ord-b90be2df3acf4395a27e8988e5b1b8b5
出典データセット
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09415049B2

反応ノート

読み込み中…

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