Diisopropylethylamine → Tert-butyl (3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)carbamate

HRID 2284641Notes

Reaction equation

HRID 2284641 reaction equation
[CH2:1]([NH:4][C:5]1[C:10]([C:11]([OH:13])=O)=[CH:9][N:8]=[C:7]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[N:6]=1)[CH2:2][CH3:3].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:55]([NH:62][CH2:63][CH2:64][CH2:65][NH2:66])([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56].C(=O)([O-])O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH2:1]([NH:4][C:5]1[C:10]([C:11]([NH:66][CH2:65][CH2:64][CH2:63][NH:62][C:55](=[O:56])[O:57][C:58]([CH3:60])([CH3:59])[CH3:61])=[O:13])=[CH:9][N:8]=[C:7]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[N:6]=1)[CH2:2][CH3:3]

Participants

9

Reactant 6

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 27960291-Hydroxybenzotriazole hydrateHCID 900517164-(Propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxylic acid

Product 1

HCID 90052194Tert-butyl (3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)carbamateYield 70.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To 4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxylic acid (A3, 452 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (575 mg) and 1-hydroxybenzotriazole monohydrate (405 mg), N,N-dimethylformamide (10 mL) was added at room temperature, and the mixture was stirred at 40° C. for 2 hours. The reaction mixture was cooled to room temperature, then N,N-diisopropylethylamine (765 μL) and N-Boc-1,3-propanediamine (330 mg) were added to the mixture, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 95% ethyl acetate in methanol) to obtain tert-butyl (3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)carbamate (B3, 481 mg) as white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at the same temperature for 2 hours
  3. customThe organic layer was separated
  4. washwashed successively with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 95% ethyl acetate in methanol)

Sources & evidence

ORD record
ord-9e0e1579d3294fb09594726cbbb3355c
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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