1,2-Dichloroethane → HCID 178499185, compound

HRID 1453872Notes

Reaction equation

HRID 1453872 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:18]([OH:20])=O)=[N:11][NH:12][C:13]=1[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH:37]([OH:41])[CH2:38][NH:39][CH3:40])[CH:32]=1.C(N(CC)CC)C.C(Cl)CCl>CN(C=O)C>[CH3:40][N:39]([CH2:38][CH:37]([OH:41])[C:33]1[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=1)[C:18]([C:10]1[NH:11][N:12]=[C:13]([C:14]([O:16][CH3:17])=[O:15])[C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:20]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 224987342-(Methylamino)-1-(pyridin-3-yl)ethan-1-olHCID 57528495Methyl 4-benzyloxy-3-carboxy-1H-pyrazole-5-carboxylate

Product 1

HCID 178499185HCID 178499185, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 4-benzyloxy-3-carboxy-1H-pyrazole-5-carboxylate (2.0 g, 7.24 mmol) in DMF (30 mL) were added HOBT (1.17 g, 8.69 mmol), 1-(3-pyridyl)-2-methylaminoethanol (1.21 g, 7.96 mmol; prepared by the methods of Tsushima, S., et al., EP 278621 and Cudahy, M. M., et al., WO 2003059911), triethylamine (0.88 g, 8.69 mmol), and EDC (1.67 g, 8.69 mmol). The reaction mixture was stirred at ambient temperature for 18 hours. The DMF was removed in vacuo and the residue was purified by prep HPLC (Waters prep LC 4000 System using a Waters Nova Pak column (3 100×40 mm I.D. cartridges, C18, 6 μM pore size) eluting with 95-5% water (0.10% TFA)/acetonitrile (0.10% TFA) at 60 mL/minute). Appropriate fractions were combined and the solvent was removed under reduced pressure to give a yellow solid. The free base of the product was obtained by partitioning between aqueous NaHCO3 and ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to give a gum. ES MS (M+1)=277.

Workup

  1. customprepared by the methods of Tsushima, S
  2. customThe DMF was removed in vacuo
  3. customthe residue was purified by prep HPLC (Waters prep LC 4000 System
  4. washeluting with 95-5% water (0.10% TFA)/acetonitrile (0.10% TFA) at 60 mL/minute)
  5. customthe solvent was removed under reduced pressure
  6. customto give a yellow solid
  7. customThe free base of the product was obtained
  8. customby partitioning between aqueous NaHCO3 and ethyl acetate
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a gum

Sources & evidence

ORD record
ord-7651b38dc7a64c048eee27ff523bc7a2
Source dataset
uspto-grants-2009_01
Patent number
US07476666B2

Reaction notes

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