1-Hydroxybenzotriazole → HCID 59224655, compound

HRID 1811750Notes

Reaction equation

HRID 1811750 reaction equation
[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([S:19][CH2:20][CH2:21][NH2:22])[N:16]=[C:15]([NH2:23])[N:14]=2)[C:10]([CH3:24])=[CH:9][C:8]=1[CH3:25])([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][C:32]([NH:34][CH:35]([CH2:39][CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:36](O)=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].C(C(N)C(O)=O)CN.Cl.Cl.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([S:19][CH2:20][CH2:21][NH:22][C:36](=[O:37])[CH:35]([NH:34][C:32]([O:31][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:33])[CH2:39][CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[N:16]=[C:15]([NH2:23])[N:14]=2)[C:10]([CH3:24])=[CH:9][C:8]=1[CH3:25])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27243292,4-Diaminobutyric acid dihydrochlorideHCID 14160003HCID 14160003, compoundHCID 59224687HCID 59224687, compound

Product 1

HCID 59224655HCID 59224655, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-[2-Amino-6-(2-aminoethylsulfanyl)pyrimidin-4-yl]-2,4-dimethylbenzoic acid tert-butyl ester (1.9 g, 5.10 mmol) obtained in Step 1 above, DL-2,4-bis((tert-butoxycarbonyl)amino)butyric acid (which can be prepared from commercially available DL-2,4-diaminobutyric acid dihydrochloride by the method described in Journal of Inorganic Biochemistry (2004) 98(11): 1933-1946) (4.9 g, 15.3 mmol), and 1-hydroxybenzotriazole (2.1 g, 15.3 mmol) were dissolved in N,N-dimethylformamide (40 ml). 1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (2.9 g, 15.3 mmol) and diisopropylethylamine (3.6 ml, 20.4 mmol) were added to the solution, and stirred overnight at room temperature. The reaction solution was diluted with ethyl acetate (400 ml), and then sequentially washed with a saturated aqueous sodium bicarbonate solution (300 ml), water (300 ml, three times), and a saturated aqueous sodium chloride solution (300 ml). After the organic layer was dried over anhydrous sodium sulfate (50 g), the inorganic salt was filtered and washed with ethyl acetate. The filtrate and washing solution were combined together, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=40:1) to yield 5-{2-amino-6-[2-(2,4-bis-tert-butoxycarbonylaminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2,4-dimethylbenzoic acid tert-butyl ester (3.2 g) as a white solid material.

Workup

  1. washsequentially washed with a saturated aqueous sodium bicarbonate solution (300 ml), water (300 ml, three times)
  2. dry with materialAfter the organic layer was dried over anhydrous sodium sulfate (50 g)
  3. filtrationthe inorganic salt was filtered
  4. washwashed with ethyl acetate
  5. washThe filtrate and washing solution
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=40:1)

Sources & evidence

ORD record
ord-5eda42d1bcdb4c86835b1e822902a0e3
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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