2-(Benzenesulfonyl)-3-phenyloxaziridine → Ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472880Notes

Reaction equation

HRID 472880 reaction equation
C(=O)=[O:2].CC(C)=O.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:18][C:19]1[N:24]2[N:25]=[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=3)[C:27]([CH3:28])=[C:23]2[N:22]=[C:21]([CH3:36])[C:20]=1[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39].C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[Cl:18][C:19]1[N:24]2[N:25]=[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=3)[C:27]([CH3:28])=[C:23]2[N:22]=[C:21]([CH3:36])[C:20]=1[CH:37]([OH:2])[C:38]([O:40][CH2:41][CH3:42])=[O:39]

Participants

6

Reactant 4

HCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 18522661Acetone cardiceHCID 86670290Ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 86670291Ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetateYield 51.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To a cold (−78° C. dry ice/acetone) stirred solution of 0.91 M KHMDS in THF (32 ml, 29.1 mmol) in additional THF (100 ml) was added ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (8.3 g, 21.94 mmol) in THF (100 ml), by dropwise addition over 30 min. The mixture was stirred for 20 min, and then a solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (7.45 g, 28.5 mmol) in THF (50 ml) was added. The reaction was stirred for 2.5 hrs at −78° C. The orange reaction mixture was quenched with sat. NH4Cl (100 mL), diluted with EtOAc (300 mL), washed with water (200 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated to give a yellow solid. The crude residue was loaded onto a flash silica gel column and eluted with 10%-30% EtOAc in hexanes. Product fractions were pooled and concentrated under reduced pressure, affording ethyl 2-(7-chloro-2-(3-chlorophenyl)-3,5-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (5.4 g, 11.40 mmol, 51.9% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ: 7.89-7.84 (m, 1H), 7.74 (dt, J=7.2, 1.6 Hz, 1H), 7.44-7.36 (m, 2H), 5.73 (s, 1H), 4.32-4.26 (m, 2H), 3.65 (br. s., 1H), 2.63 (s, 3H), 2.51 (s, 3H), 1.24 (t, J=7.02 Hz, 3H). LCMS (M+H)=394.06.

Workup

  1. additionby dropwise addition over 30 min
  2. stirringThe reaction was stirred for 2.5 hrs at −78° C
  3. customThe orange reaction mixture was quenched with sat. NH4Cl (100 mL)
  4. additiondiluted with EtOAc (300 mL)
  5. washwashed with water (200 mL), brine (100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow solid
  10. washeluted with 10%-30% EtOAc in hexanes
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b7b3ce68f5604e2db4705f23bf88e51e
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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