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

HRID 472860Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 472860
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

Komponenten

8

Edukt 4

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

Produkt 1

HCID 66693072Methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateAusbeute 30,4 %

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 (0.072 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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8e57d8566ddb4f8881186b36ed20d6f5
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08633200B2

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