1,2-Dichloroethane → Methyl(2S)-2-({[1-ethyl-4-(tetrahydro-2H-pyranylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}amino)-3-hydroxypropanoate

HRID 490888Notes

Reaction equation

HRID 490888 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:19]([OH:21])=O)[C:11]([NH:12][CH:13]3[CH2:18][CH2:17]OCC3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[CH2:22](Cl)[CH2:23]Cl.C1C=CC2N([OH:35])N=NC=2C=1.Cl.[CH3:37][O:38][C:39](=[O:44])[C@H:40]([CH2:42][OH:43])[NH2:41].C(N(CC)CC)C>CN(C=O)C>[CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:19]([NH:41][C@@H:40]([CH2:42][OH:43])[C:39]([O:38][CH3:37])=[O:44])=[O:21])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][CH2:23][CH2:22][O:35]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 534878291-Ethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid

Product 1

HCID 69060926Methyl(2S)-2-({[1-ethyl-4-(tetrahydro-2H-pyranylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]carbonyl}amino)-3-hydroxypropanoateYield 41.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate 17 (0.1 g, 0.34 mmol), EDC (0.066 g, 0.34 mmol) and HOBT (0.05 g, 0.37 mmol) were suspended in DMF (2 ml) and stirred at room temperature under nitrogen for 15 mins. L-Serine methyl ester hydrochloride (0.054 g, 0.34 mmol) and triethylamine (0.036 g, 0.36 mmol) were added and the mixture stirred at room temperature under nitrogen for 18 hours. Solvents were removed in vacuo and the residue was partitioned between DCM and water. The organic layer was concentrated in vacuo and applied to an SPE cartridge (aminopropyl, 5 g), which was eluted with methanol. Concentration in vacuo afforded an impure residue which was further purified by SPE cartridge (silica, 5 g), eluting with ethyl acetate followed by 5% methanol/ethyl acetate. The desired fractions were concentrated in vacuo to afford Intermediate 33 (0.055 g). LCMS showed MH+=393; TRET=2.22 min.

Workup

  1. stirringthe mixture stirred at room temperature under nitrogen for 18 hours
  2. customSolvents were removed in vacuo
  3. customthe residue was partitioned between DCM and water
  4. concentrationThe organic layer was concentrated in vacuo
  5. washwas eluted with methanol
  6. concentrationConcentration in vacuo
  7. customafforded an impure residue which
  8. customwas further purified by SPE cartridge (silica, 5 g)
  9. washeluting with ethyl acetate
  10. concentrationThe desired fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-f33bb98ccb944af5be77a4433196179c
Source dataset
uspto-grants-2009_05
Patent number
US07528148B2

Reaction notes

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