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 490906노트

반응식

HRID 490906 반응식
[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]

참가 물질

6

반응물 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

생성물 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}hydrazinecarboxylate수율 54.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-0217dacf751c49ba8379064153d94e85
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07528148B2

반응 노트

불러오는 중…