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

HRID 472864노트

반응식

HRID 472864 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.[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

참가 물질

8

반응물 4

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

생성물 1

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

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 (0.036 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.

후처리

  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

출처 및 근거

ORD 기록
ord-b333f77b9abd438bb5ea5ab046f04eff
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633200B2

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