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 490906Notes

Reaction equation

HRID 490906 reaction equation
[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]

Participants

6

Reactant 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

Product 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}hydrazinecarboxylateYield 54.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-0217dacf751c49ba8379064153d94e85
Source dataset
uspto-grants-2009_05
Patent number
US07528148B2

Reaction notes

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