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

HRID 472856노트

반응식

HRID 472856 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.[Li+].[Cl-].C1COCC1.[CH2:27]([Mg]Cl)[CH:28]([CH3:30])[CH3:29].C1COCC1.C([Mg]Cl)C(C)C.Cl[C:45](=[O:50])[C:46]([O:48][CH3:49])=[O:47]>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:45](=[O:50])[C:46]([O:48][CH3:49])=[O:47])=[C:7]([CH2:27][CH:28]([CH3:30])[CH3:29])[N:6]3[N:9]=2)[CH:17]=[CH:16][CH:15]=1

참가 물질

8

반응물 5

HCID 79846Methyl chloroglyoxylateHCID 68902752LiCl THFHCID 866702846-Bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidineHCID 178418368HCID 178418368, 화합물HCID 178420649HCID 178420649, 화합물

생성물 1

HCID 66691806Methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate수율 34%

시약·촉매·용매 2

HCID 24593copper(I) bromide촉매HCID 3283Diethyl Ether용매

실험 절차

To a stirred solution of 6-bromo-7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidine (0.179 g, 0.5 mmol), copper(I) bromide (0.036 g, 0.250 mmol) and 0.5M LiCl/THF (8 ml, 4.00 mmol) was added 2M i-BuMgCl/THF (2.000 ml, 4.00 mmol) over 5 min at rt. After 2 h, LCMS indicated presence of mostly the unreacted starting material. More iBuMgCl (1 ml) was added and continued stirring at rt for additional 4 h and methyl 2-chloro-2-oxoacetate (0.736 ml, 8.00 mmol) added at once to the reaction mixture, and stirred for additional 1 h. 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)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.0772 g, 0.170 mmol, 34.0% yield) as yellow oil which turned to yellow solid overtime and contaminated with about 15% of 2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidine. 1H NMR (500 MHz, CDCl3) δ: 7.98 (d, J=1.8 Hz, 1H), 7.87-7.83 (m, 1H), 7.41-7.31 (m, 2H), 6.87 (s, 1H), 3.97 (s, 3H), 3.13 (d, J=7.3 Hz, 2H), 2.51 (s, 3H), 2.44 (dt, J=13.7, 6.8 Hz, 1H), 0.97 (d, J=6.7 Hz, 6H). LCMS (M+H) calcd for C20H21ClN3O3: 386.13. found: 386.3.

후처리

  1. stirringstirred for additional 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-394b6fd3f0e4414fbb7a1a268e828fd9
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633200B2

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