1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178433765, compound

HRID 2282225Notes

Reaction equation

HRID 2282225 reaction equation
Cl.Cl.[CH3:3][C:4]1[C:16]([C:17]2[S:18][C:19]([C:28]3[N:32]=[CH:31][NH:30][N:29]=3)=[C:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:21]=2)=[C:7]2[CH:8]=[C:9]([O:12][CH2:13][CH2:14][NH2:15])[CH:10]=[CH:11][N:6]2[N:5]=1.C(OC([NH:40][C:41]([CH3:46])([CH3:45])[C:42](O)=[O:43])=O)(C)(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CCOC(C)=O.O.CN(C=O)C>[NH2:40][C:41]([CH3:46])([CH3:45])[C:42]([NH:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[CH:11][N:6]2[N:5]=[C:4]([CH3:3])[C:16]([C:17]3[S:18][C:19]([C:28]4[N:32]=[CH:31][NH:30][N:29]=4)=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:21]=3)=[C:7]2[CH:8]=1)=[O:43]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 178433763HCID 178433763, compound

Product 1

HCID 178433765HCID 178433765, compoundYield 45.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-({2-methyl-3-[4-phenyl-5-(1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyrazolo[1,5-a]pyridin-5-yl}oxy)ethanamine di-hydrochloride (100 mg, 0.20 mmol) obtained in Example 73-B(i), TEA (1.5 mL), 2-[(tert-butoxycarbonyl)amino]-2-methylpropanoic acid (75 mg, 0.37 mmol), HOBT (50 mg, 0.37 mmol), EDCI (210 mg, 1.1 mmol) and DMF (20 mL) was stirred at rt for 14 h. To the reaction mixture were added water (200 mL) and EtOAc (200 mL) and the mixture was stirred for 30 min. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. To a solution of the above residue in MeOH (10 mL) and THF (15 mL) was added 6N hydrochloric acid (3 mL), and the mixture was stirred at 70° C. for 1 h. The reaction mixture was allowed to cool to rt and then the solvent was evaporated. To the reaction mixture were added EtOAc (100 mL), 8N aqueous sodium hydroxide solution (3 mL) and water (100 mL), and the mixture was stirred for 30 min. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was washed with diisopropyl ether and dried to give the title compound (46 mg, 45%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 30 min
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customInsoluble materials were removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionTo a solution of the above residue in MeOH (10 mL) and THF (15 mL) was added 6N hydrochloric acid (3 mL)
  7. stirringthe mixture was stirred at 70° C. for 1 h
  8. temperatureto cool to rt
  9. customthe solvent was evaporated
  10. additionTo the reaction mixture were added EtOAc (100 mL), 8N aqueous sodium hydroxide solution (3 mL) and water (100 mL)
  11. stirringthe mixture was stirred for 30 min
  12. washThe organic layer was washed with brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customInsoluble materials were removed by filtration
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. washThe residue was washed with diisopropyl ether
  17. customdried

Sources & evidence

ORD record
ord-67d90d7ef82b4f9cb49b2ee68a25d120
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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