Hydrochloric Acid → 1-trityl-1H-[1,2,4]triazole-3-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 720635Notes

Reaction equation

HRID 720635 reaction equation
[C:1]([N:20]1[CH:24]=[N:23][C:22]([C:25](O)=[O:26])=[N: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:22]2[N:23]=[CH:24][N:20]([C:1]([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)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:21]=2)=[O:26])=[CH:68][CH:69]=1)=[O:71]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 21891680N-{6-Amino-1-butyl-3-[(2-fluorophenyl)methyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl}-2-(4-aminophenyl)acetamideHCID 218918071-trityl-1H-[1,2,4]triazole-3-carboxylic acid

Product 1

HCID 587392261-trityl-1H-[1,2,4]triazole-3-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 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-trityl-1H-[1,2,4]triazole-3-carboxylic acid (51 mg, 0.65 mmol) in N,N-dimethylformamide (0.8 mL) at 25° C. was treated with 1-hydroxybenzotriazole hydrate (19.3 mg, 0.14 mmol) and O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophosphate (54 mg, 0.14 mmol). The resulting mixture was cooled to 0° C. and then treated with the hydrochloric acid salt of 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 (62 mg, 0.13 mmol) and N,N-diisopropylethylamine (0.11 mL, 0.65 mmol). The reaction was stirred at 0° C. for 1 h and then at 25° C. for 4.5 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL) and washed with a saturated aqueous sodium bicarbonate solution (1×15 mL) and a saturated aqueous sodium chloride solution (1×20 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–00 mesh, 93:7 dichloromethane/methanol) afforded 1-trityl-1H-[1,2,4]triazole-3-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 (67.9 mg, 68%) as a pale yellow solid: FAB-HRMS m/e calcd for C45H41N8O4F (M+Na)+ 799.3133, found 799.3113.

Workup

  1. waitat 25° C. for 4.5 h
  2. concentrationAt this time, the reaction was concentrated in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (50 mL)
  4. washwashed with a saturated aqueous sodium bicarbonate solution (1×15 mL)
  5. dry with materialThe organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0c180090a4fa4b75b65edb00b767db13
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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