Sodium Carbonate → (S)-methyl 2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472867ノート

反応式

HRID 472867 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:29]=[C:11]3[N:12]=[C:13]([CH3:28])[C:14]([C:22](=[O:27])[C:23]([O:25][CH3:26])=[O:24])=[C:15]([CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]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.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:29]=[C:11]3[N:12]=[C:13]([CH3:28])[C:14]([C@H:22]([OH:27])[C:23]([O:25][CH3:26])=[O:24])=[C:15]([CH:16]4[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 15900295catecholborane THFHCID 66693087Methyl 2-(2-(3-chlorophenyl)-7-cyclohexyl-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 66692981(S)-methyl 2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate収率 83%

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-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (0.094 g, 0.205 mmol) in toluene (3 mL) was added 1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (0.041 ml, 0.041 mmol) at rt and cooled to −35° C. To this was added dropwise 1M catecholborane/THF (0.288 ml, 0.288 mmol) over 10 min. After stirring 30 min, the reaction mixture was slowly warm to −15° C. over 30 min and diluted with EtOAc (15 mL). Then, the mixture was vigorously stirred with sat Na2CO3 (2 mL) for 45 min. The aq layer separated and org layer washed with sat sat Na2CO3 (2×5 mL), dried (Na2SO4), filtered, concentrated and the resulting yellow residue purified by prep-HPLC to afford (S)-methyl 2-(2-(3-chlorophenyl)-7-cyclohexyl-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (0.0705 g, 0.170 mmol, 83% yield) as yellow solid. LCMS (M+H) calcd for C22H25ClN3O3: 414.16. found: 414.3.

後処理

  1. temperaturethe reaction mixture was slowly warm to −15° C. over 30 min
  2. customThe aq layer separated
  3. washorg layer washed
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe resulting yellow residue purified by prep-HPLC

出典と根拠

ORDレコード
ord-f1a00e161a534c21a9b17bef8b347184
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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