3-Pyridinemethanamine → N-(4-Methyl-3-{1-methyl-2-oxo-7-[(pyridin-3-ylmethyl)-amino]-1,2-dihydro-[1,6]naphthyridin-3-yl}-phenyl)-3-trifluoromethyl-benzamide

HRID 270715ノート

反応式

HRID 270715 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.[NH2:34][CH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=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>[CH3:20][C:19]1[CH:18]=[CH:17][C:16]([NH:21][C:22](=[O:33])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:32])[F:31])[CH:24]=2)=[CH:15][C:14]=1[C:7]1[C:8](=[O:13])[N:9]([CH3:12])[C:10]2[C:5]([CH:6]=1)=[CH:4][N:3]=[C:2]([NH:34][CH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1)[CH:11]=2

参加物

5

反応物 3

HCID 310183-PyridinemethanamineHCID 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 59833940N-(4-Methyl-3-{1-methyl-2-oxo-7-[(pyridin-3-ylmethyl)-amino]-1,2-dihydro-[1,6]naphthyridin-3-yl}-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 (50 mg, 0.106 mmol) is mixed with 3-(aminomethyl)-pyridine (18 mg, 0.16 mmol), Pd2(dba)2 (2.4 mg, 2.5%), 1,3-Bis(2,6-di-i-propylphenyl)-imidazolium chloride (2.3 mg, 5%) and potassium tert-butanoxide (17.8 mg, 0.159 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 final product as a pale solid: 1H NMR 400 MHz (DMSO-d6) δ 10.46 (s, 1H), 8.79 (s, 1H), 8.68 (d, 1H, J=4.6 Hz), 8.44 (s, 1H), 8.29 (s, 1H), 8.24 (t, 2H, J=7.5 Hz), 7.96 (d, 2H, J=7.8 Hz), 7.76 (m, 3H), 7.65 (m, 2H), 7.24 (d, 1H, J=8.3 Hz), 6.46 (s, 1H), 4.74 (s, 2H), 3.52 (s, 3H), 2.11 (s, 3H); MS m/z 544.3 (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-303fec6bc46e41e98819c7cf2db26445
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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