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 574352Notes

Reaction equation

HRID 574352 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-eb07d68293734b82be2afc042138cf3c
Source dataset
uspto-grants-2015_05
Patent number
US09034882B2

Reaction notes

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