1,2-Dichloroethane → 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-4-carboxamide

HRID 42453ノート

反応式

HRID 42453 の反応式
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C:20](O)=[O:21])[C:6]2[C:7]([CH3:19])=[C:8]([CH2:15][N:16]([CH3:18])[CH3:17])[N:9]([CH:12]([CH3:14])[CH3:13])[C:10]=2[CH:11]=1.[NH2:23][CH2:24][C:25]1[C:26](=[O:35])[NH:27][C:28]([CH3:34])=[CH:29][C:30]=1[CH2:31][CH2:32][CH3:33].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C)C=O.ClCCl>[Cl:2][C:3]1[CH:4]=[C:5]([C:20]([NH:23][CH2:24][C:25]2[C:26](=[O:35])[NH:27][C:28]([CH3:34])=[CH:29][C:30]=2[CH2:31][CH2:32][CH3:33])=[O:21])[C:6]2[C:7]([CH3:19])=[C:8]([CH2:15][N:16]([CH3:18])[CH3:17])[N:9]([CH:12]([CH3:13])[CH3:14])[C:10]=2[CH:11]=1

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 671241403-(Aminomethyl)-6-methyl-4-propylpyridin-2(1H)-oneacetateHCID 674684516-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid hydrochloride salt

生成物 1

HCID 674642276-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-4-carboxamide収率 63.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid hydrochloride salt (0.42 g, 1.216 mmol), 3-(aminomethyl)-6-methyl-4-propylpyridin-2(1H)-one (0.22 g, 1.221 mmol), HOAt (0.17 g, 1.249 mmol) was added Dichloromethane (16 mL), N,N-Dimethylformamide (4 mL) and N-methylmorpholine (135 μL, 1.228 mmol). The mixture was stirred and EDC free base (0.20 g, 1.288 mmol) was added. After stirring for 2 hr LCMS showed that the reaction was complete. The reaction was evaporated to dryness under vacuum and purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 8% (5% NH4OH in MeOH) in CH2Cl2). The pure fractions were combined, evaporated to dryness then taken up in 20% EtOAc in hexanes. Scratching crystallized out the product which was filtered and washed with hexanes to give the product 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indole-4-carboxamide (362 mg, 0.769 mmol, 63.2% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=11.49 (s, 1H), 8.24 (t, J=4.9 Hz, 1H), 7.61 (d, J=1.8 Hz, 1H), 6.83 (d, J=1.8 Hz, 1H), 5.89 (s, 1H), 4.91 (quin, J=7.0 Hz, 1H), 4.31 (d, J=5.1 Hz, 2H), 3.47 (s, 2H), 2.52 (2H under DMSO), 2.14 (s, 6H), 2.12 (s, 3H), 2.10 (s, 3H), 1.62-1.53 (m, 2H), 1.51 (d, J=7.1 Hz, 6H), 0.94 (t, J=7.3 Hz, 3H). MS (ES)+m/e 471.3 [M+H]+.

後処理

  1. stirringAfter stirring for 2 hr LCMS
  2. customThe reaction was evaporated to dryness under vacuum
  3. custompurified by silica gel chromatography (Analogix
  4. customevaporated to dryness
  5. customScratching crystallized out the product which
  6. filtrationwas filtered
  7. washwashed with hexanes

出典と根拠

ORDレコード
ord-5d5cde2001eb478ebcf28f6c3a95491f
出典データセット
uspto-grants-2013_09
特許番号
US08536179B2

反応ノート

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