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

HRID 472852Notes

Reaction equation

HRID 472852 reaction equation
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.[CH:20]([Mg]Cl)([CH3:22])[CH3:21].[Li+].[Cl-].C1COCC1.Cl[C:33](=[O:38])[C:34]([O:36][CH3:37])=[O:35]>[Cu]Br.C1COCC1>[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:33](=[O:38])[C:34]([O:36][CH3:37])=[O:35])=[C:7]([CH:20]([CH3:22])[CH3:21])[N:6]3[N:9]=2)[CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 79846Methyl chloroglyoxylateHCID 866702846-Bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidineHCID 178420665HCID 178420665, compound

Product 1

HCID 66692217Methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateYield 14.7%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A 100 mL RB-flask was charged with 6-bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (0.918 g, 2.57 mmol) and copper(I) bromide (0.092 g, 0.643 mmol) was added anhydrous THF (30 mL). To the resulting mixture was added 1M iPrMgCl—LiCl/THF (3.34 ml, 3.34 mmol) over 5 min. After 1 h, methyl 2-chloro-2-oxoacetate (0.501 ml, 5.45 mmol) was added at once to the dark reaction mixture and stirred for additional 1 h. Then, the resulting homogeneous orange brown reaction mixture was quenched with sat NaHCO3 (1 mL), diluted with Et2O (75 mL), washed with water (2×25 mL), brine (25 mL), dried (Na2SO4/C), filtered and concentrated to give yellow residue. This residue was purified on silica gel column using 5-30% EtOAc/Hex (5% increment per 500 mL) to give methyl 2-(2-(3-chlorophenyl)-7-isopropyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.1402 g, 0.377 mmol, 14.67% yield) as yellow solid; 1H NMR (500 MHz, CDCl3) δ: 8.01-7.98 (m, 1H), 7.87 (dt, J=7.0, 1.7 Hz, 1H), 7.43-7.38 (m, 2H), 6.87 (s, 1H), 3.98 (s, 3H), 3.43-3.34 (m, 1H), 2.47 (s, 3H), 1.62 (d, J=7.0 Hz, 6H). LCMS (M+H) calcd for C17H16N3O2: 372.11. found: 372.2.

Workup

  1. customonce to the dark reaction mixture
  2. customThen, the resulting homogeneous orange brown reaction mixture was quenched with sat NaHCO3 (1 mL)
  3. additiondiluted with Et2O (75 mL)
  4. washwashed with water (2×25 mL), brine (25 mL)
  5. dry with materialdried (Na2SO4/C)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give yellow residue
  9. customThis residue was purified on silica gel column

Sources & evidence

ORD record
ord-cafd8168c108410b935af212dc85c40c
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

Loading…