Benzylamine → HCID 22921561, compound

HRID 2258630Notes

Reaction equation

HRID 2258630 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[N:7]([CH:8]([CH3:12])[C:9](O)=O)[C:6]2[CH:13]=[C:14]([N:18]3[C:23](=[O:24])[CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[N:20]([CH3:29])[C:19]3=[O:30])[C:15]([F:17])=[CH:16][C:5]=2[N:4]=1.[OH:33]N1C2C=CC=CC=2N=N1.Cl.CN(C)[CH2:46][CH2:47][CH2:48][N:49]=[C:50]=NCC.[C:55]1(CN)C=C[CH:58]=[CH:57][CH:56]=1>C(Cl)Cl.O>[C:47]1([CH2:48][NH:49][C:50]([CH2:9][CH:8]([N:7]2[C:6]3[CH:13]=[C:14]([N:18]4[C:23](=[O:24])[CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[N:20]([CH3:29])[C:19]4=[O:30])[C:15]([F:17])=[CH:16][C:5]=3[N:4]=[C:3]2[C:2]([F:31])([F:32])[F:1])[CH3:12])=[O:33])[CH:46]=[CH:58][CH:57]=[CH:56][CH:55]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22921548HCID 22921548, compound2×

Product 1

HCID 22921561HCID 22921561, compoundYield 58.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, a solution of 0.7 gram (0.0015 mole) of 2-[2-trifluoromethyl-5-fluoro-6-(1-methyl-6-trifluoromethyluracil-3-yl)benzimidazol-1-yl]propanoic acid (Compound 19--prepared as in Step B of Example 8) in 20 mL of methylene chloride was stirred, and 0.4 gram (0.0030 mole) of 1-hydroxybenzotriazole, then 0.5 gram (0.0030 mole) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added. The reaction mixture was cooled to about 0° C., and 0.2 gram (0.0015 mole) of N-(phenylmethyl)amine was added. Upon completion of the addition, the reaction mixture was allowed to warm to ambient temperature, where it stirred for about 72 hours. The reaction mixture was then poured into water and extracted with methylene chloride. The combined extracts were washed with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil, which was subjected to column chromatography on silica gel, with 1:2 ethyl acetate/hexane as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.5 gram of N-phenylmethyl-2-[2-trifluoromethyl-5-fluoro-6-(1-methyl-6-trifluoromethyluracil-3-yl)benzimidazol-1-yl]propanecarboxamide; mp 191°-193° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of the addition
  2. temperatureto warm to ambient temperature
  3. extractionextracted with methylene chloride
  4. washThe combined extracts were washed with an aqueous solution saturated with sodium chloride
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure to a residual oil, which
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-000590e8de704fd092bb7551b353f0e6
Source dataset
uspto-grants-1997_08
Patent number
US05661108

Reaction notes

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