Benzylamine → N-[3-(7-Benzylamino-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-4-methyl-phenyl]-3-trifluoromethyl-benzamide

HRID 270717ノート

反応式

HRID 270717 の反応式
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:15]=[C:16]([NH:21][C:22](=[O:33])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)[CH:17]=[CH:18][C:19]=3[CH3:20])[C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][N:3]=1.[CH2:34]([NH2:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C>O1CCOCC1>[CH2:34]([NH:41][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:15]=[C:16]([NH:21][C:22](=[O:33])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:31])([F:30])[F:32])[CH:24]=4)[CH:17]=[CH:18][C:19]=3[CH3:20])[C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][N:3]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

参加物

5

反応物 3

HCID 7504BenzylamineHCID 27349131,3-Bis(2,6-diisopropylphenyl)imidazolium chlorideHCID 59833848Benzamide,n-[3-(7-chloro-1,2-dihydro-1-methyl-2-oxo-1,6-naphthyridin-3-yl)-4-methylphenyl]-3-(trifluoromethyl)-

生成物 1

HCID 59833796N-[3-(7-Benzylamino-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-4-methyl-phenyl]-3-trifluoromethyl-benzamide

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

N-[3-(7-Chloro-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-4-methyl-phenyl]-3-trifluoromethyl-benzamide (100 mg, 0.21 mmol) is mixed with benzylamine (35 mg, 0.32 mmol), Pd2(dba)2 (4.8 mg, 2.5%), 1,3-Bis(2,6-di-i-propylphenyl)imidazolium chloride (4.6 mg, 5%) and potassium tert-butanoxide (35.6 mg, 0.32 mmol) under an argon environment. 6 mL of anhydrous 1,4-dioxane is added and the reaction is continued at 100° C. for 14 hours. After cooling and removal of solvent under vacuum, the crude product is dissolved in DMSO and purified by reverse phase preparative HPLC to give the product N-[3-(7-Benzylamino-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-4-methyl-phenyl]-3-trifluoromethyl-benzamide as pale solid. This product is dissolved into 10 mL of ethanol and 8 mg of 10% palladium carbon powder is added. The reaction is stirred at room temperature under a 50 psi hydrogen environment for 16 hours. After passing through a celite plug to remove the palladium carbon and removing the solvent, the crude product is dissolved in DMSO and purified by reverse phase preparative HPLC to give the final product as a white solid: 1H NMR 400 MHz (DMSO-d6) δ 10.42 (s, 1H), 8.35 (s, 1H), 8.31 (s, 1H), 8.26 (d, 1H, J=7.8 Hz), 7.96 (d, 1H, J=7.7 Hz), 7.78 (t, 1H, J=7.8 Hz), 7.69 (m, 2H), 7.61 (s, 1H), 7.24 (d, 1H, J=8.1 Hz), 6.53 (s, 2H), 6.29 (s, 1H), 3.49 (s, 3H), 2.12 (s, 3H); MS m/z 453.2 (M+1).

後処理

  1. temperatureAfter cooling
  2. customremoval of solvent under vacuum
  3. dissolutionthe crude product is dissolved in DMSO
  4. custompurified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-eca030e2c06741b396c65311759da871
出典データセット
uspto-grants-2008_11
特許番号
US07449582B2

反応ノート

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