Triethylamine → 1-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methyl cyclopropanecarboxylate

HRID 1399338Notes

Reaction equation

HRID 1399338 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]([CH:25]2[CH2:27][CH2:26]2)[OH:24])=[CH:4][CH:3]=1.[CH:28]1([C:31](O)=[O:32])[CH2:30][CH2:29]1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+]>CN(C)C1C=CN=CC=1.O1CCCC1>[CH:28]1([C:31]([O:24][CH:23]([CH:25]2[CH2:27][CH2:26]2)[C:5]2[C:6]3[N:7]4[CH2:14][CH2:13][CH2:12][N:11]([C:15]5[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=5[Cl:22])[C:8]4=[N:9][C:10]=3[C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:32])[CH2:30][CH2:29]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 15655Cyclopropanecarboxylic acidHCID 25517Ammonium ChlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57786088[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methanol

Product 1

HCID 577862541-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methyl cyclopropanecarboxylateYield 67%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](cyclopropyl)methanol (200 mg, 0.473 mmol), cyclopropanecarboxylic acid (61 mg, 0.710 mmol), triethylamine (0.132 mL, 0.946 mmol) and 4-dimethylaminopyridine (87 mg, 0.710 mmol) in tetrahydrofuran (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (181 mg, 0.946 mmol) at room temperature. The mixture was stirred at room temperature for 15 hr. Saturated aqueous ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 10-50% ethyl acetate/n-hexane gradient mixture and recrystallization from ethanol to give the title compound (155 mg, 0.316 mmol, 67%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with 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 10-50% ethyl acetate/n-hexane gradient mixture and recrystallization from ethanol

Sources & evidence

ORD record
ord-8de0db50ce1e4dfba609fcd4deadd0fc
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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