Water → HCID 68415195, compound

HRID 1811745Notes

Reaction equation

HRID 1811745 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][O:11][C:12](=[O:32])[C:13]1[CH:18]=[C:17]([C:19]2[CH:24]=[C:23]([S:25][CH2:26][CH2:27][NH2:28])[N:22]=[C:21]([NH2:29])[N:20]=2)[C:16]([CH3:30])=[CH:15][C:14]=1[CH3:31].[C:33]([O:37][C:38](NCCCC(O)=O)=[O:39])([CH3:36])([CH3:35])[CH3:34].O[N:48]1[C:52]2[CH:53]=[CH:54]C=C[C:51]=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[OH2:69]>CN(C)C=O>[CH3:10][O:11][C:12](=[O:32])[C:13]1[CH:18]=[C:17]([C:19]2[CH:24]=[C:23]([S:25][CH2:26][CH2:27][NH:28][C:54](=[O:69])[CH2:53][CH:52]([NH:48][C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[CH3:51])[N:22]=[C:21]([NH2:29])[N:20]=2)[C:16]([CH3:30])=[CH:15][C:14]=1[CH3:31]

Participants

8

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59224712HCID 59224712, compound

Product 1

HCID 68415195HCID 68415195, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (0.59 ml, 3.39 mmol) was added to an N,N-dimethylformamide (2.7 ml) solution of 5-[2-amino-6-(2-aminoethylsulfanyl)pyrimidin-4-yl]-2,4-dimethylbenzoic acid methyl ester (225 mg, 0.68 mmol) obtained in Step 2 above, 4-tert-butoxycarbonylaminobutanoic acid (165 mg, 0.81 mmol), N-hydroxybenzotriazole (93 mg, 0.69 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (262 mg, 1.37 mmol). The resulting mixture was stirred at room temperature for 2.5 hours. Water was added to the reaction solution, and extracted twice with ethyl acetate. The organic layers were combined together, and then sequentially washed with water and a saturated aqueous sodium chloride solution. The ethyl acetate solution was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1) to yield 5-{2-amino-6-[2-(3-tert-butoxycarbonylaminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2,4-dimethylbenzoic acid methyl ester (257 mg, 73%) as a white solid.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washsequentially washed with water
  3. dry with materialThe ethyl acetate solution was dried over anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1)

Sources & evidence

ORD record
ord-ee1851da7c064386a8f23783e4df98dd
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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