Triethylamine → N-{1-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propyl}-2,2-difluoroacetamide

HRID 1399323Notes

Reaction equation

HRID 1399323 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([NH2:26])[CH2:24][CH3:25])=[CH:4][CH:3]=1.[F:27][CH:28]([F:32])[C:29](O)=[O:30].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([NH:26][C:29](=[O:30])[CH:28]([F:32])[F:27])[CH2:24][CH3:25])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 9788Difluoroacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 577863351-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-amine

Product 1

HCID 57786293N-{1-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propyl}-2,2-difluoroacetamideYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-amine (150 mg, <0.366 mmol), difluoroacetic acid (0.0346 mL, 0.55 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (158 mg, 0.824 mmol), 1-hydroxybenzotriazole monohydrate (126 mg, 0.823 mmol) and triethylamine (0.15 mL, 1.07 mmol) in N,N-dimethylformamide (5.0 mL) was stirred at room temperature for 5 days. Water was added to the reaction mixture at room temperature and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 25-75% ethyl acetate/n-hexane gradient mixture and recrystallization from ethyl acetate/diisopropyl ether to give the title compound (56.3 mg, 0.115 mmol, 32%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel eluting with a 25-75% ethyl acetate/n-hexane gradient mixture and recrystallization from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-bacf251bb0be47c9a8f1f44af2057a57
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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