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 270715노트

반응식

HRID 270715 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.[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

참가 물질

5

반응물 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)-

생성물 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

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-(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).

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-303fec6bc46e41e98819c7cf2db26445
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07449582B2

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