2-(Benzenesulfonyl)-3-phenyloxaziridine → Methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 574352노트

반응식

HRID 574352 반응식
[Br:1][C:2]1[CH:24]=[C:5]2[N:6]=[C:7]([CH3:23])[C:8]([CH2:18][C:19]([O:21][CH3:22])=[O:20])=[C:9]([N:10]3[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[CH2:12][CH2:11]3)[N:4]2[N:3]=1.CC([OH:28])C.C(=O)=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[Br:1][C:2]1[CH:24]=[C:5]2[N:6]=[C:7]([CH3:23])[C:8]([CH:18]([OH:28])[C:19]([O:21][CH3:22])=[O:20])=[C:9]([N:10]3[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[CH2:12][CH2:11]3)[N:4]2[N:3]=1

참가 물질

6

반응물 4

HCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86586944Isopropanol carbon dioxideHCID 86695077HCID 86695077, 화합물

생성물 1

HCID 86695078Methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate수율 82%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (1.49 g, 3.79 mmol, 1 equiv) in THF (38 mL) at −78° C. (IPA/CO2) was added KHMDS (6.8 mL of a 0.91M solution in THF, 6.07 mmol, 1.6 equiv). The reaction turned a deep orange color. After 15 min, 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (1.49 g, 5.69 mmol, 1.5 equiv) was added in a single portion. The reaction solution significantly darkened and was then allowed to stir for 30 min. The reaction was then removed from the cooling bath and quenched with saturated aqueous solution of NaHCO3, added to water, and extracted with EtOAc (×3). The combined EtOAc extracts were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (0-100% EtOAc/hexane) to provide methyl 2-(2-bromo-7-(4,4-dimethylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate as a waxy yellow solid (1.28 g, 82%). 1H NMR (400 MHz, CDCl3) δ 6.57 (s, 1H), 5.53 (d, J=5.3 Hz, 1H), 4.78 (br. s., 1H), 4.52 (d, J=5.3 Hz, 1H), 3.80 (s, 3H), 2.60 (s, 3H), 1.57-1.53 (m, J=3.8 Hz, 4H), 1.10 (s, 6H); LCMS (ESI, M+1): 411.2.

후처리

  1. customThe reaction was then removed from the cooling bath
  2. customquenched with saturated aqueous solution of NaHCO3
  3. additionadded to water
  4. extractionextracted with EtOAc (×3)
  5. dry with materialThe combined EtOAc extracts were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel flash chromatography (0-100% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-eb07d68293734b82be2afc042138cf3c
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034882B2

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