Diisopropylethylamine → 1-trityl-1H-imidazole-4-carboxylic acid (4-{[6-amino-1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-amide

HRID 720640Notes

Reaction equation

HRID 720640 reaction equation
[C:1]([N:20]1[CH:24]=[C:23]([C:25](O)=[O:26])[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.Cl.[NH2:40][C:41]1[N:46]([CH2:47][CH2:48][CH2:49][CH3:50])[C:45](=[O:51])[N:44]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[F:59])[C:43](=[O:60])[C:42]=1[NH:61][C:62](=[O:71])[CH2:63][C:64]1[CH:69]=[CH:68][C:67]([NH2:70])=[CH:66][CH:65]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[NH2:40][C:41]1[N:46]([CH2:47][CH2:48][CH2:49][CH3:50])[C:45](=[O:51])[N:44]([CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[F:59])[C:43](=[O:60])[C:42]=1[NH:61][C:62]([CH2:63][C:64]1[CH:65]=[CH:66][C:67]([NH:70][C:25]([C:23]2[N:22]=[CH:21][N:20]([C:1]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:24]=2)=[O:26])=[CH:68][CH:69]=1)=[O:71]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 105701171-Trityl-1H-imidazole-4-carboxylic acidHCID 21891679n-[6-Amino-1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-(4-amino-phenyl)-acetamide hydrochloride salt

Product 1

HCID 587392571-trityl-1H-imidazole-4-carboxylic acid (4-{[6-amino-1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-amideYield 111.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-trityl-1H-imidazole-4-carboxylic acid (67 mg, 0.19 mmol) in N,N-dimethylformamide (1.0 mL) at 25 ° C. was treated with 1-hydroxybenzotriazole hydrate (25.4 mg, 0.19 mmol) and O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophosphate (71 mg, 0.19 mmol). This solution was cooled to 0° C. and then was treated with N-[6-amino-1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-(4-amino-phenyl)-acetamide hydrochloride salt (81.5 mg, 0.17 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.85 mmol). The reaction was stirred at 0° C. for 1 h and then at 25° C. for 4 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (1×25 mL). Some residual solids were then removed by filtration. The filtrate was washed with a saturated aqueous sodium chloride solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 1-trityl-1H-imidazole-4-carboxylic acid (4-{[6-amino-1-butyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-methyl}-phenyl)-amide (147 mg, quant.) as a pale yellow foam: LR-MS for C23H18N2O2 (M−H)+ at m/z=353.

Workup

  1. waitat 25° C. for 4 h
  2. concentrationAt this time, the reaction was concentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. washwas washed with a saturated aqueous sodium bicarbonate solution (1×25 mL)
  5. customSome residual solids were then removed by filtration
  6. washThe filtrate was washed with a saturated aqueous sodium chloride solution
  7. dry with materialThe organics were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3e76b9ccbc5c44b4883abb79b71f61ce
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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