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

HRID 472864Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 472864
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

Komponenten

8

Edukt 4

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

Produkt 1

HCID 66693787Methyl 2-(2-(3-chlorophenyl)-5-methyl-7-(p-tolyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateAusbeute 24,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24593copper(I) bromideKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b333f77b9abd438bb5ea5ab046f04eff
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08633200B2

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