Diisopropylethylamine → HCID 117864629, compound

HRID 1486324Notes

Reaction equation

HRID 1486324 reaction equation
[F:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15](O)=[O:16])=[C:10]2[CH:9]=[C:8]([O:19][CH3:20])[CH:7]=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:57][CH2:58][C:59]([NH:64][C:65](=[O:71])[O:66][C:67]([CH3:70])([CH3:69])[CH3:68])([CH3:63])[CH2:60][CH2:61][CH3:62]>O1CCCC1>[C:67]([O:66][C:65](=[O:71])[NH:64][C:59]([CH3:63])([CH2:60][CH2:61][CH3:62])[CH2:58][NH:57][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[C:21]([F:25])=[CH:22][CH:23]=[CH:24][C:2]=3[F:1])=[CH:7][C:8]([O:19][CH3:20])=[CH:9][C:10]=12)=[O:16])([CH3:70])([CH3:69])[CH3:68]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 84723920rac-tert-Butyl (1-amino-2-methylpentan-2-yl)carbamateHCID 117859583HCID 117859583, compound

Product 1

HCID 117864629HCID 117864629, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 170 mg (0.366 mmol, 75% purity) of 7-[(2,6-difluorobenzyl)oxy]-5-methoxy-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid (Example 163A) in 8 ml of tetrahydrofuran was admixed with 84 mg (0.44 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS: 25952-53-8) and 60 mg (0.44 mmol) of 1-hydroxy-7-azabenzotriazole (CAS: 39968-33-7). The solution was stirred at room temperature for 20 minutes. The reaction mixture was admixed with 0.191 ml (1.01 mmol) of N,N-diisopropylethylamine and 158 mg (0.732 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester (Example 152A). The mixture was stirred at room temperature for a further 18 hours, and the reaction mixture was then concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was removed, extracted with a saturated aqueous sodium hydrogencarbonate solution, water and aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated under reduced pressure. The remaining residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:dichloromethane/methanol, gradient 0% to 10%), which gave 120 mg (44% yield, 73% purity) of product.

Workup

  1. stirringThe mixture was stirred at room temperature for a further 18 hours
  2. concentrationthe reaction mixture was then concentrated under reduced pressure
  3. customThe residue was partitioned between dichloromethane and water
  4. customThe organic phase was removed
  5. extractionextracted with a saturated aqueous sodium hydrogencarbonate solution, water and aqueous sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe remaining residue was purified by flash chromatography
  10. customgave 120 mg (44% yield, 73% purity) of product

Sources & evidence

ORD record
ord-45d5aeafdd4b4ff2a7e67347d8abdc68
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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