Diisopropylethylamine → 1-methyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amide

HRID 720646Notes

Reaction equation

HRID 720646 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[NH:15][C:14]3[C:13](=[O:16])[N:12]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])[C:11](=[O:25])[N:10]([CH2:26][CH:27]4[CH2:29][CH2:28]4)[C:9]=3[N:8]=2)=[CH:4][CH:3]=1.[CH3:32][N:33]1[CH:37]=[C:36]([C:38](O)=[O:39])[CH:35]=[N:34]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:27]1([CH2:26][N:10]2[C:9]3[N:8]=[C:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([NH:1][C:38]([C:36]5[CH:35]=[N:34][N:33]([CH3:32])[CH:37]=5)=[O:39])=[CH:31][CH:30]=4)[NH:15][C:14]=3[C:13](=[O:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:11]2=[O:25])[CH2:28][CH2:29]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6431601-Methyl-1H-pyrazole-4-carboxylic acidHCID 218917373-Cyclopropylmethyl-8-[4-aminobenzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione

Product 1

HCID 104145581-methyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amideYield 21.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 8-(4-amino-benzyl)-3-cyclopropylmethyl-1-(2-fluoro-benzyl)-3,7-dihydro-purine-2,6-dione (50 mg, 0.12 mmol) in N,N-dimethylformamide at 25° C. was treated with a solution of 1-methyl-1H-pyrazole-4-carboxylic acid (15 mg, 0.12 mmol), O-benzotriazol-1-yl-N,N.N′N′-tetramethyluronium hexafluorophosphate (49.7 mg, 0.13 mmol), and N,N-diisopropylethylamine (62 μL, 0.36 mmol). The resulting solution was stirred at 25° C. for 18 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in chloroform and then was washed with a 1N aqueous hydrochloric acid solution (1×10 mL) and a saturated aqueous sodium chloride solution (1×10 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 760mesh, 5:95 methanol/dichloromethane) afforded 1-methyl-1H-pyrazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amide (13.5 mg, 21.5%) as a tan solid: EI-HRMS m/e calcd for C28H26N7O3 (M+) 527.2081, found 527.2083.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. dissolutionThe residue was dissolved in chloroform
  3. washwas washed with a 1N aqueous hydrochloric acid solution (1×10 mL)
  4. dry with materialThe organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-30e8f53c90de4087b60c375ed1242f69
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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