Dimethylformamide → 3-hydroxy-1-methyl-2-{2,2,2-trifluoro-1-[methyl(prop-2-yn-1-yl)amino]ethyl}pyridin-4(1H)-one

HRID 1519040ノート

反応式

HRID 1519040 の反応式
CN(C=O)C.C(Cl)(=O)C(Cl)=O.[OH:12][C:13]1[C:18](=[O:19])[CH:17]=[CH:16][N:15]([CH3:20])[C:14]=1[CH:21](O)[C:22]([F:25])([F:24])[F:23].CCN(CC)CC.[CH3:34][NH:35][CH2:36][C:37]#[CH:38]>C(#N)C>[OH:12][C:13]1[C:18](=[O:19])[CH:17]=[CH:16][N:15]([CH3:20])[C:14]=1[CH:21]([N:35]([CH3:34])[CH2:36][C:37]#[CH:38])[C:22]([F:25])([F:24])[F:23]

参加物

7

反応物 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 96160N-methylpropyn-2-ylamineHCID 67282261HCID 67282261、化合物

生成物 1

HCID 866728123-hydroxy-1-methyl-2-{2,2,2-trifluoro-1-[methyl(prop-2-yn-1-yl)amino]ethyl}pyridin-4(1H)-one収率 46.4%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To 20 mL acetonitrile cooled in an ice-water bath was added DMF (0.42 mL, 5.4 mmol) followed by oxalyl chloride (0.47 mL, 5.4 mmol) dropwise. To this resulting suspension was added 3-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one (1.0 g, 4.5 mmol) in one portion. The mixture was then stirred for 2 h. Then, Et3N (2.50 mL, 17.9 mmol) was added to this reaction mixture followed by N-methyl propargylamine (0.75 mL, 9.0 mmol). The reaction mixture was stirred at RT for overnight. The solid was filtered off, and the filtrate was concentrated to dryness. The residue was purified by flash chromatography on silica gel (5% MeOH in CH2Cl2 as eluant) to afford the title compound, Apo7057 (570 mg) as an orange powder. Yield=46.4%; 1H NMR (400 MHz, DMSO+a few drops of D2O) δ (ppm): 7.6 (br. s., 1H), 6.25 (d, J=7.1 Hz, 1H), 5.15 (br. s., 1H), 3.87 (s, 3H), 3.37-3.67 (m, 2H), 3.23 (br. s., 1H), 2.32 (br. s., 3H); MS m/z 275 [M+1]+, 206 (100%).

後処理

  1. stirringThe reaction mixture was stirred at RT for overnight
  2. filtrationThe solid was filtered off
  3. concentrationthe filtrate was concentrated to dryness
  4. customThe residue was purified by flash chromatography on silica gel (5% MeOH in CH2Cl2 as eluant)

出典と根拠

ORDレコード
ord-74549448097648eba36a76674f383928
出典データセット
uspto-grants-2015_07
特許番号
US09073865B2

反応ノート

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