Sodium Carbonate → (S)-methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472857노트

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HRID 472857 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:27]=[C:11]3[N:12]=[C:13]([CH3:26])[C:14]([C:20](=[O:25])[C:21]([O:23][CH3:24])=[O:22])=[C:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.[B]1OC2C(=CC=CC=2)O1.C1COCC1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:27]=[C:11]3[N:12]=[C:13]([CH3:26])[C:14]([C@H:20]([OH:25])[C:21]([O:23][CH3:24])=[O:22])=[C:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 15900295catecholborane THFHCID 66691806Methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole toluene

생성물 1

HCID 66693831(S)-methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate수율 90%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
-35 °C

실험 절차

To a stirred solution of methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.077 g, 0.170 mmol) in toluene (3 mL) was added 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.034 ml, 0.034 mmol) at rt and cooled to −35° C. To this was added dropwise 1M catecholborane/THF (0.237 ml, 0.237 mmol) over 10 min. After stirring 30 min, the reaction mixture was slowly warm to −15° C. over 30 min and diluted with EtOAc (15 mL). Then, the mixture was vigorously stirred with sat Na2CO3 (2 mL) for 45 min. The aqueous layer separated and organic layer washed with sat sat Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated and the resulting yellow residue purified by prep-HPLC to afford (S)-methyl 2-(2-(3-chlorophenyl)-7-isobutyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.0592 g, 0.153 mmol, 90% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ: 7.98 (t, J=1.7 Hz, 1H), 7.85 (dt, J=7.3, 1.5 Hz, 1H), 7.40-7.32 (m, 2H), 6.80 (s, 1H), 5.52 (s, 1H), 3.81 (s, 3H), 3.66 (br. s., 1H), 3.34-3.23 (m, 2H), 2.51 (s, 3H), 2.43 (dt, J=13.6, 6.9 Hz, 1H), 1.05 (d, J=6.7 Hz, 6H). LCMS (M+H) calcd for C20H23ClN3O3: 388.14. found: 388.3.

후처리

  1. temperaturethe reaction mixture was slowly warm to −15° C. over 30 min
  2. customThe aqueous layer separated
  3. washorganic layer washed
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe resulting yellow residue purified by prep-HPLC

출처 및 근거

ORD 기록
ord-2238bc8bdaf64867beec64248ea56328
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08633200B2

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