catecholborane THF → (S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472861ノート

反応式

HRID 472861 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C:23](=[O:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.[B]1OC2C(=CC=CC=2)O1.C1COCC1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:30]=[C:11]3[N:12]=[C:13]([CH3:29])[C:14]([C@H:23]([OH:28])[C:24]([O:26][CH3:27])=[O:25])=[C:15]([C:16]4[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 3

HCID 15900295catecholborane THFHCID 66693072Methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole toluene

生成物 1

HCID 66692935(S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate収率 94%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-35 °C

実験手順

To a stirred solution of methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.083 g, 0.196 mmol) in toluene (5 mL) was added 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.039 ml, 0.039 mmol) and cooled to −35° C. To this was added dropwise 1M catecholborane/THF (0.294 ml, 0.294 mmol) over 10 min and stirred for additional 20 min. Then, the reaction was slowly warmed to −15 C over 30 min, diluted with EtOAc (10 ml) and quenched with sat. Na2CO3 (5 mL). The resulting mixture was vigorously stirred for 30 min, aq. larer removed and organic layer washed with sat. Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated to yellow residue which was purified by prep-HPLC to afford (S)-methyl 2-(2-(3-chlorophenyl)-7-(4-fluorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.08 g, 0.184 mmol, 94% yield) as solid. 1H NMR (500 MHz, CDCl3) δ: 7.82 (s, 1H), 7.75-7.68 (m, 1H), 7.68-7.58 (m, 2H), 7.34-7.24 (m, 4H), 6.88 (s, 1H), 5.16 (s, 1H), 3.78 (s, 3H), 3.69-3.34 (br.s., 1H), 2.58 (s, 3H). LCMS (M+H) calcd for C22H18ClFN3O3: 426.1. found: 426.2.

後処理

  1. temperatureThen, the reaction was slowly warmed to −15 C over 30 min
  2. customquenched with sat. Na2CO3 (5 mL)
  3. stirringThe resulting mixture was vigorously stirred for 30 min
  4. customaq. larer removed
  5. washorganic layer washed with sat. Na2CO3 (2×5 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated to yellow residue which
  9. customwas purified by prep-HPLC

出典と根拠

ORDレコード
ord-e03cfafa2aac43ccabaca70be5cf8d10
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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