1,2-Dichloroethane → 1,1-Dimethylethyl 2-{[1-ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}hydrazinecarboxylate

HRID 490906ノート

反応式

HRID 490906 の反応式
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH3:22])=[C:10]([C:19]([OH:21])=O)[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:37]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])(=[O:40])[NH:38][NH2:39]>CN(C=O)C>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH3:22])=[C:10]([C:19]([NH:39][NH:38][C:37]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:21])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

参加物

6

反応物 4

HCID 111,2-DichloroethaneHCID 70091tert-Butyl carbazateHCID 757711-HydroxybenzotriazoleHCID 576751871-Ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid

生成物 1

HCID 576752221,1-Dimethylethyl 2-{[1-ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}hydrazinecarboxylate収率 54.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Intermediate 60 (0.253 g, 0.83 mmol), EDC (0.223 g, 1.17 mmol) and HOBT (0.135 g, 1.0 mmol) in DMF (5 ml) was stirred at 20° C. for 30 minutes. t-Butyl carbazate (0.110 g, 0.83 mmol) was added and stirring continued for 18 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in DMF (5 ml) additional EDC (0.159 g0) and HOBT (0.112 g) added. After 30 minutes t-butyl carbazate (0.019 g) was added and stirring continued for 18 hours. The reaction was concentrated in vacuo and the residue partitioned between DCM and water. The organic phase was washed with aqueous sodium hydrogen carbonate then evaporated in vacuo. The material was applied to a SPE cartridge (silica, 10 g) and eluted with cyclohexane:ethyl acetate (1:1 followed by 2:1) to afford Intermediate 62 as a white solid (0.19 g). LCMS showed MH+=419; TRET=2.35 min.

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in DMF (5 ml) additional EDC (0.159 g0)
  3. additionHOBT (0.112 g) added
  4. additionAfter 30 minutes t-butyl carbazate (0.019 g) was added
  5. stirringstirring
  6. waitcontinued for 18 hours
  7. concentrationThe reaction was concentrated in vacuo
  8. customthe residue partitioned between DCM and water
  9. washThe organic phase was washed with aqueous sodium hydrogen carbonate
  10. customthen evaporated in vacuo
  11. washeluted with cyclohexane:ethyl acetate (1:1 followed by 2:1)

出典と根拠

ORDレコード
ord-0217dacf751c49ba8379064153d94e85
出典データセット
uspto-grants-2009_05
特許番号
US07528148B2

反応ノート

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