Methyl chloroglyoxylate → Methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

HRID 472864ノート

反応式

HRID 472864 の反応式
Br[C:2]1[C:3]([CH3:19])=[N:4][C:5]2[N:6]([N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[CH:11]=2)[C:7]=1Cl.[C:20]1([CH3:28])[CH:25]=[CH:24][C:23]([Mg]Br)=[CH:22][CH:21]=1.C1COCC1.[Li+].[Cl-].C1COCC1.Cl[C:42](=[O:47])[C:43]([O:45][CH3:46])=[O:44]>C1COCC1.CCOCC.[Cu]Br>[Cl:18][C:14]1[CH:13]=[C:12]([C:10]2[CH:11]=[C:5]3[N:4]=[C:3]([CH3:19])[C:2]([C:42](=[O:47])[C:43]([O:45][CH3:46])=[O:44])=[C:7]([C:23]4[CH:24]=[CH:25][C:20]([CH3:28])=[CH:21][CH:22]=4)[N:6]3[N:9]=2)[CH:17]=[CH:16][CH:15]=1

参加物

8

反応物 4

HCID 79846Methyl chloroglyoxylateHCID 68902752LiCl THFHCID 866702846-Bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidineHCID 178420639HCID 178420639、化合物

生成物 1

HCID 66693787Methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate収率 24.6%

試薬・触媒・溶媒 3

HCID 24593copper(I) bromide触媒HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred mixture of 6-bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (0.179 g, 0.5 mmol) and copper(I) bromide (0.036 g, 0.250 mmol) in THF (3 mL) was added dropwise over 10 min a pre-mixed solution of 1M p-tolylmagnesiumbromide/THF (3.00 ml, 3.00 mmol) and 0.5M LiCl/THF (6.00 ml, 3.00 mmol) at rt. After 2.5 h, methyl 2-chloro-2-oxoacetate (0.552 ml, 6 mmol) was added at once and stirred overnight at rt. Then, the reaction was diluted with Et2O (50 mL), quenched with Na2CO3 (1 mL), washed with 10 mL each water and brine, dried (Na2SO4), filtered and concentrated to give orange paste which was purified by prep-HPLC to afford methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.103 g, 0.123 mmol, 24.53% yield) as yellow solid which is contaminated with impurity. 1H NMR (500 MHz, CDCl3) δ: 7.95 (d, J=0.9 Hz, 1H), 7.81 (td, J=4.4, 1.5 Hz, 1H), 7.62 (d, J=8.2 Hz, 2H), 7.40 (d, J=7.6 Hz, 2H), 7.38-7.36 (m, 2H), 6.99 (s, 1H), 3.39 (s, 3H), 2.71 (s, 3H), 2.71 (s, 3H). LCMS (M+H) calcd for C23H19ClFN3O3: 420.11. found: 420.2.

後処理

  1. customquenched with Na2CO3 (1 mL)
  2. washwashed with 10 mL each water and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give orange paste which
  7. customwas purified by prep-HPLC

出典と根拠

ORDレコード
ord-b333f77b9abd438bb5ea5ab046f04eff
出典データセット
uspto-grants-2014_01
特許番号
US08633200B2

反応ノート

読み込み中…