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

HRID 2208963ノート

反応式

HRID 2208963 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([N:12]([CH2:20][CH3:21])[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.Cl.[NH2:24][CH2:25][C:26]1[C:27](=[O:37])[NH:28][C:29]([CH3:36])=[CH:30][C:31]=1[C:32]([F:35])([F:34])[F:33].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>[Cl:1][C:2]1[CH:3]=[C:4]([N:12]([CH2:20][CH3:21])[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:5]([CH3:11])=[C:6]([CH:10]=1)[C:7]([NH:24][CH2:25][C:26]1[C:27](=[O:37])[NH:28][C:29]([CH3:36])=[CH:30][C:31]=1[C:32]([F:33])([F:34])[F:35])=[O:9]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 708738575-Chloro-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methylbenzoic acidHCID 901508353-(Aminomethyl)-6-methyl-4-(trifluoromethyl)-1,2-dihydropyridin-2-one hydrochloride HCl salt

生成物 1

HCID 708741785-Chloro-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-N-{[6-methyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]methyl}benzamide収率 42%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
23 °C

実験手順

To a stirred solution of 5-chloro-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methylbenzoic acid (crude material, ˜0.7 mmol) and 3-(aminomethyl)-6-methyl-4-(trifluoromethyl)-1,2-dihydropyridin-2-one hydrochloride HCl salt (200 mg, 0.91 mmol) in DMSO (5.3 mL) was added PyBOP (550 mg, 1.05 mmol) and hunig base (366 ul, 2.10 mmol). The reaction mixture was stirred at 23° C. for 7 hours. The reaction mixture was quenched with water and diluted with ethylacetate. The aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (SiO2 Ethylacetate/MeOH=10/1+5% triethylamine). The crude compound was triturated with ethylacetate/hexane, and dried to give the titled compound as a white solid (145 mg, 42% yield). 1H-NMR (400 MHz, CDCl3) δppm; 7.08 (d, J=2.4 Hz, 1H), 7.03 (d, J=2.4 Hz, 1H), 6.81-6.85 (m, 1H), 6.35 (s, 1H), 4.71 (d, J=5.2 Hz, 2H), 3.03 (q, J=6.8 Hz, 2H), 2.81-2.85 (m, 2H), 2.68-2.72 (m, 1H), 2.39 (s, 3H), 2.27 (s, 3H), 2.24 (s, 3H), 1.88-1.94 (m, 2H), 1.67-1.72 (m, 4H), 0.85 (t, J=6.8 Hz, 3H); MS (ES) [M+H] 499.1, [M+Na] 521.1; HPLC 96.0% purity.

後処理

  1. customThe reaction mixture was quenched with water
  2. additiondiluted with ethylacetate
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (SiO2 Ethylacetate/MeOH=10/1+5% triethylamine)
  9. customThe crude compound was triturated with ethylacetate/hexane
  10. customdried

出典と根拠

ORDレコード
ord-8cbca89225e644e9a9c4c288770a3a6a
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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