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

HRID 472880ノート

反応式

HRID 472880 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒4 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-b7b3ce68f5604e2db4705f23bf88e51e
出典データセット
uspto-grants-2014_01
特許番号
US08633200B2

反応ノート

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