Methyl chloroglyoxylate → Methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate

HRID 472860ノート

反応式

HRID 472860 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.[F:20][C:21]1[CH:26]=[CH:25][C:24]([Mg]Br)=[CH:23][CH:22]=1.CCOCC.[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:24]4[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=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 178467878HCID 178467878、化合物

生成物 1

HCID 66693072Methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate収率 30.4%

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 (0.072 g, 0.500 mmol) in THF (3 mL) was added dropwise a pre-mixed solution of 2M 4-fluorophenylmagnesium bromide/ether (3.00 ml, 6.00 mmol) and 0.5M LiCl/THF (6.00 ml, 3.00 mmol) over 15 min. After 2 h, added at once methyl 2-chloro-2-oxoacetate (0.368 ml, 4.00 mmol) to the dark solution. After 1 h, 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)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.0644 g, 0.152 mmol, 30.4% yield) as yellow solid contaminated with some impurity. 1H NMR (500 MHz, CDCl3) δ: 7.88 (s, 1H), 7.81-7.74 (m, 1H), 7.73-7.67 (m, 2H), 7.35 (d, J=5.2 Hz, 2H), 7.31-7.24 (m, 2H), 6.97 (s, 1H), 3.44 (s, 3H), 2.67 (s, 3H). LCMS (M+H) calcd for C22H16ClFN3O3: 424.09. found: 424.3. LCMS (M+H) calcd for C22H16ClFN3O3: 424.09. found: 424.3.

後処理

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

出典と根拠

ORDレコード
ord-8e57d8566ddb4f8881186b36ed20d6f5
出典データセット
uspto-grants-2014_01
特許番号
US08633200B2

反応ノート

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