2-(Benzenesulfonyl)-3-phenyloxaziridine → Ethyl 7-chloro-6-(2-ethoxy-1-hydroxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 921067Notes

Reaction equation

HRID 921067 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:11][C:12]1[N:17]2[N:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:20]=[C:16]2[N:15]=[C:14]([CH3:26])[C:13]=1[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].C1(C2[O:41]N2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[Cl:11][C:12]1[N:17]2[N:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:20]=[C:16]2[N:15]=[C:14]([CH3:26])[C:13]=1[CH:27]([OH:41])[C:28]([O:30][CH2:31][CH3:32])=[O:29]

Participants

5

Reactant 3

HCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86691584Ethyl 7-chloro-6-(2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

Product 1

HCID 117604925Ethyl 7-chloro-6-(2-ethoxy-1-hydroxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylateYield 54.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 0.9M KHMDS (40.9 mL, 36.8 mmol) in THF (100 mL) at −78° C. was added a THF (50 mL) solution of ethyl 7-chloro-6-(2-ethoxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (10 g, 30.7 mmol, for synthesis see WO2013025584) was added over the course of 20 min. After 30 min, a THF (15 mL) solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (10.43 g, 39.9 mmol) was added to the red reaction mixture and stirring was continued for an additional 30 min at −78° C. Then, the resulting orange reaction mixture was quenched with sat. aq. NH4Cl (50 mL), diluted with EtOAc (200 mL), washed with water (100 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo to give a solid. This solid was triturated with small amount of ethyl acetate and solids were filtered, washed with hexanes and dried under high vacuum to afford ethyl 7-chloro-6-(2-ethoxy-1-hydroxy-2-oxoethyl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (5 g, 16.85 mmol, 43% yield, 90% pure) as light yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.21 (s, 1H), 5.76 (s, 1H), 4.58-4.49 (m, 2H), 4.33 (dtt, J=10.7, 7.1, 3.7 Hz, 2H), 2.71-2.64 (s, 3H), 1.48 (t, J=7.2 Hz, 3H), 1.29-1.24 (m, 3H). LCMS (M+1)=342.16.

Workup

  1. additionwas added over the course of 20 min
  2. waitwas continued for an additional 30 min at −78° C
  3. customThen, the resulting orange reaction mixture was quenched with sat. aq. NH4Cl (50 mL)
  4. additiondiluted with EtOAc (200 mL)
  5. washwashed with water (100 mL), brine (100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a solid
  10. customThis solid was triturated with small amount of ethyl acetate and solids
  11. filtrationwere filtered
  12. washwashed with hexanes
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-bd132856f58445f1873349cdf3b69d2a
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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