1-Hydroxybenzotriazole → N-(2-aminoethyl)-3-(6-(4-hydroxy-3-methylphenyl)-2-oxo-2,3-dihydropyrimidin-4-yl)benzamide

HRID 422061Notes

Reaction equation

HRID 422061 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:15]3[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=3)[C:18]([OH:20])=O)[NH:11][C:12](=[O:14])[N:13]=2)=[CH:4][C:3]=1[CH3:24].[NH2:25][CH2:26][CH2:27][NH:28]C(=O)OC(C)(C)C.ON1C2C=CC=CC=2N=N1.CCN=C=NCCC[N+](C)(C)C.[I-]>ClC(Cl)C.CN(C)C=O>[NH2:25][CH2:26][CH2:27][NH:28][C:18](=[O:20])[C:17]1[CH:21]=[CH:22][CH:23]=[C:15]([C:10]2[NH:11][C:12](=[O:14])[N:13]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([OH:1])=[C:3]([CH3:24])[CH:4]=3)[CH:9]=2)[CH:16]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1222421-(3-(Dimethylamino)propyl)-3-ethylcarbodiimide methiodideHCID 187201N-BOC-ethylenediamineHCID 1784225943-(6-(4-Hydroxy-3-methylphenyl)-2-oxo-2,3-dihydropyrimidin-4-yl)benzoic acid

Product 1

HCID 178422593N-(2-aminoethyl)-3-(6-(4-hydroxy-3-methylphenyl)-2-oxo-2,3-dihydropyrimidin-4-yl)benzamideYield 23.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 3-(6-(4-hydroxy-3-methylphenyl)-2-oxo-2,3-dihydropyrimidin-4-yl)benzoic acid obtained from step 2 of Example 57 (16.9 mg, 48 μmol) and tert-butyl 2-aminoethylcarbamate (6.4 mg, 40 μmol) in dichloroethane (1.25 mL) and N,N-dimethylformamide (0.79 mL) was added 1-hydroxybenzotriazole (6.8 mg, 50 μmol) followed by 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide methiodide (17.8 mg, 60 μmol). The resultant mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated in vacuo, taken up in methanol (1 mL) and 4.0 N hydrochloric acid in dioxane (1 mL), and stirred at room temperature for 4 hours then concentrated. Purification of the residue by HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) followed by concentration in vacuo gave the title compound N-(2-aminoethyl)-3-(6-(4-hydroxy-3-methylphenyl)-2-oxo-2,3-dihydropyrimidin-4-yl)benzamide (3.4 mg, 23%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. concentrationthen concentrated
  3. customPurification of the residue by HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid)
  4. concentrationfollowed by concentration in vacuo

Sources & evidence

ORD record
ord-2ccdc60d5ba84f5193c6ee78a7202e42
Source dataset
uspto-grants-2012_01
Patent number
US08101625B2

Reaction notes

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