N-(tert-butoxycarbonyl)glycine → Tert-butyl (2-oxo-2-((3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)amino)ethyl)carbamate

HRID 2284643Notes

Reaction equation

HRID 2284643 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:9]([NH:23][CH2:24][CH2:25][CH3:26])=[N:10][C:11]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[N:12][CH:13]=1)=[O:7].[C:27]([NH:34][CH2:35][C:36](O)=[O:37])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O>[O:37]=[C:36]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:9]([NH:23][CH2:24][CH2:25][CH3:26])=[N:10][C:11]([NH:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[N:12][CH:13]=1)=[O:7])[CH2:35][NH:34][C:27](=[O:28])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33]

Participants

9

Reactant 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 90052165N-(3-aminopropyl)-4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamide

Product 1

HCID 90052168Tert-butyl (2-oxo-2-((3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)amino)ethyl)carbamateYield 101.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To N-(3-aminopropyl)-4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamide (B4, 57 mg), N-Boc-glycine (44 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (127 mg) and 1-hydroxybenzotriazole monohydrate (102 mg), N,N-dimethylformamide (2 mL) and triethylamine (46 μL) were added at room temperature, and the mixture was stirred at the same temperature for 7 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 95 to 90% ethyl acetate in methanol) to obtain amorphous tert-butyl (2-oxo-2-((3-(4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxamido)propyl)amino)ethyl)carbamate (B5, 83 mg).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. washwashed successively with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 95 to 90% ethyl acetate in methanol)

Sources & evidence

ORD record
ord-5acda82367284268a9f721b145b40e61
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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