Diisopropylethylamine → HCID 66898270, compound

HRID 1519055Notes

Reaction equation

HRID 1519055 reaction equation
Cl.[CH2:2]([O:9][C:10]1[C:11](=[O:19])[CH:12]=[C:13]([CH2:17]Cl)[N:14]([CH3:16])[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH2:20][C@H:21]([C:23]([NH:25][CH3:26])=[O:24])[CH3:22].Cl.C(N(C(C)C)CC)(C)C>CC#N>[CH2:2]([O:9][C:10]1[C:11](=[O:19])[CH:12]=[C:13]([CH2:17][NH:20][C@@H:21]([CH3:22])[C:23]([NH:25][CH3:26])=[O:24])[N:14]([CH3:16])[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 18595779(2S)-2-amino-N-methylpropanamide hydrochlorideHCID 71755461481726-31-2

Product 1

HCID 66898270HCID 66898270, compoundYield 87.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-(benzyloxy)-2-(chloromethyl)-1-methylpyridin-4(1H)-one hydrochloride (7.55 g, 25.0 mmol), H-Ala-NHMe.HCl (5.14 g, 37.0 mmol) and diisopropylethylamine (12.5 mL, 72.0 mmol) in CH3CN (50 mL) was heated at 85° C. under a nitrogen atmosphere for overnight. Volatiles were removed in vacuo, and the residue was pre-purified by column chromatography on silica gel using a mixture of MeOH and ethyl acetate as eluant (solvent gradient of 10, 15 and 20% MeOH in ethyl acetate). The fractions rich in product were combined and evaporated to dryness. Further purification by column chromatography on silica gel using a mixture of H2O and CH3CN (1-5% H2O content) and then a 10% MeOH in dichloromethane solution afforded (S)-2-((5-(benzyloxy)-1-methyl-4-oxo-1,4-dihydropyridin-2-yl)methylamino)-N-methylpropanamide (7.17 g) in 87% yield. MS m/z 352 [M+Na]+, 330 (100%) [M+1]+, 228, 138, 91.

Workup

  1. customVolatiles were removed in vacuo
  2. customthe residue was pre-purified by column chromatography on silica gel using
  3. additiona mixture of MeOH and ethyl acetate as eluant (solvent gradient of 10, 15 and 20% MeOH in ethyl acetate)
  4. customevaporated to dryness
  5. customFurther purification by column chromatography on silica gel using
  6. additiona mixture of H2O and CH3CN (1-5% H2O content)

Sources & evidence

ORD record
ord-9135870e56324d8086eba2548e3ef74c
Source dataset
uspto-grants-2015_07
Patent number
US09073865B2

Reaction notes

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