Diisopropylethylamine → 3-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-N-{[6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]methyl}-5-(trifluoromethyl)benzamide

HRID 2208958ノート

反応式

HRID 2208958 の反応式
[CH2:1]([N:3]([CH:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)[C:4]1[C:5]([CH3:17])=[C:6]([CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1)[C:7]([OH:9])=O)[CH3:2].Cl.Cl.[NH2:27][CH2:28][C:29]1[C:30](=[O:40])[NH:31][C:32]([CH3:39])=[CH:33][C:34]=1[C:35]([F:38])([F:37])[F:36].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CS(C)=O>[CH2:1]([N:3]([CH:18]1[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]1)[C:4]1[C:5]([CH3:17])=[C:6]([CH:10]=[C:11]([C:13]([F:15])([F:16])[F:14])[CH:12]=1)[C:7]([NH:27][CH2:28][C:29]1[C:30](=[O:40])[NH:31][C:32]([CH3:39])=[CH:33][C:34]=1[C:35]([F:36])([F:37])[F:38])=[O:9])[CH3:2]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 708736533-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acidHCID 901508353-(Aminomethyl)-6-methyl-4-(trifluoromethyl)-1,2-dihydropyridin-2-one hydrochloride HCl salt

生成物 1

HCID 890527413-[Ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-N-{[6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]methyl}-5-(trifluoromethyl)benzamide収率 45%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

To a stirred solution of 3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzoic acid (crude material, ˜0.313 mmol) and 3-(aminomethyl)-6-methyl-4-(trifluoromethyl)-1,2-dihydropyridin-2-one hydrochloride HCl salt (100 mg, 0.91 mmol) in DMSO (2.4 mL) was added PyBOP (248 mg, 1.05 mmol) and hunig base (166 ul, 2.10 mmol). The reaction mixture was stirred at rt for 16 hours. The reaction mixture was quenched with water and resulting precipitate was collected. The solid was triturated from ethylacetate/hexane. The resulting solid was purified by silica gel column chromatography (NH—SiO2 ethylacetate/MeOH=10/1+10% triethylamine). The crude compound was triturated from ethylacetate/hexane, and dried to give the titled compound as a white solid (75.0 mg, 44% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.32 (s, 1H), 7.26 (s, 1H), 6.86-6.89 (m, 1H), 6.34 (s, 1H), 4.73 (d, J=6.4 Hz, 2H), 3.08 (q, J=7.2 Hz, 2H), 2.80-2.85 (m, 2H), 2.70-2.78 (m, 1H), 2.37 (s, 3H), 2.35 (s, 3H), 2.24 (s, 3H), 1.85-1.89 (m, 2H), 1.69-1.72 (m, 4H), 0.84 (t, J=7.2 Hz, 3H); MS (ES) [M+H] 533.1, [M+Na] 555.2; HPLC 95.8% purity.

後処理

  1. customThe reaction mixture was quenched with water
  2. customresulting precipitate
  3. customwas collected
  4. customThe solid was triturated from ethylacetate/hexane
  5. customThe resulting solid was purified by silica gel column chromatography (NH—SiO2 ethylacetate/MeOH=10/1+10% triethylamine)
  6. customThe crude compound was triturated from ethylacetate/hexane
  7. customdried

出典と根拠

ORDレコード
ord-e9ea2235418c489cbc74463b732be540
出典データセット
uspto-grants-2016_06
特許番号
US09376422B2

反応ノート

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