3-(4-Methylpiperazin-1-yl)aniline → N-(4-Methyl-3-{1-methyl-7-[3-(4-methyl-piperazin-1-yl)-phenylamino]-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl}-phenyl)-3-trifluoromethyl-benzamide

HRID 270716노트

반응식

HRID 270716 반응식
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.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([C:41]2[CH:42]=[C:43]([NH2:47])[CH:44]=[CH:45][CH:46]=2)[CH2:37][CH2:36]1.[Cl-].C(C1C=CC=C(CCC)C=1[N+]1C=CN(C2C(CCC)=CC=CC=2CCC)C=1)CC>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:31])[F:32])[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:47][C:43]1[CH:44]=[CH:45][CH:46]=[C:41]([N:38]3[CH2:37][CH2:36][N:35]([CH3:34])[CH2:40][CH2:39]3)[CH:42]=1)[CH:11]=2

참가 물질

5

반응물 3

HCID 115646133-(4-Methylpiperazin-1-yl)anilineHCID 223147471,3-Bis(2,6-di-1-propylphenyl)imidazolium chlorideHCID 59833848Benzamide,n-[3-(7-chloro-1,2-dihydro-1-methyl-2-oxo-1,6-naphthyridin-3-yl)-4-methylphenyl]-3-(trifluoromethyl)-

생성물 1

HCID 59833910N-(4-Methyl-3-{1-methyl-7-[3-(4-methyl-piperazin-1-yl)-phenylamino]-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl}-phenyl)-3-trifluoromethyl-benzamide

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

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-(4-Methyl-piperazin-1-yl)-phenylamine (31 mg, 0.16 mmol), Pd2(dba)2 (2.4 mg, 2.5%), 1,3-Bis(2,6-di-1-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 10.47 (s, 1H), 9.43 (s, 1H), 8.58 (s, 1H), 8.30 (s, 1H), 8.26 (d, 1H, J=8.1 Hz), 7.21 (d, 1H, J=7.9 Hz), 7.83 (s, 1H), 7.79 (t, 1H, J=7.8 Hz), 7.69 (m, 2H), 7.37 (s, 1H), 7.21 (m, 3H), 6.74 (s, 1H), 6.65 (d, 1H, J=6.5 Hz), 3.80 (d, 2H, J=13.9 Hz), 3.56 (s, 3H), 3.54 (d, 2H, J=13.9 Hz), 3.18 (m, 2H), 2.98 (m, 2H), 2.88 (d, 3H, J=3.8 Hz), 2.14 (s, 3H); MS m/z 627.3 (M+1).

후처리

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

출처 및 근거

ORD 기록
ord-69a181628f774e6aa7432db790e69d8e
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07449582B2

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