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

HRID 472860노트

반응식

HRID 472860 반응식
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

참가 물질

8

반응물 4

HCID 79846Methyl chloroglyoxylateHCID 68902752LiCl THFHCID 866702846-Bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidineHCID 178467878HCID 178467878, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 24593copper(I) bromide촉매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8e57d8566ddb4f8881186b36ed20d6f5
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633200B2

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