Hydrochloric Acid → 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-N-methoxy-N-methylpentanamide

HRID 1399313Notes

Reaction equation

HRID 1399313 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]([CH2:30][CH3:31])[CH2:24][C:25](OCC)=[O:26])=[CH:4][CH:3]=1.[OH-].[Na+].Cl.Cl.[CH3:36][NH:37][O:38][CH3:39].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>O1CCCC1.CO.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]([CH2:30][CH3:31])[CH2:24][C:25]([N:37]([O:38][CH3:39])[CH3:36])=[O:26])=[CH:4][CH:3]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57786021Ethyl 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentanoate

Product 1

HCID 577863853-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-N-methoxy-N-methylpentanamideYield 72.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentanoate (200 mg, 0.416 mmol) in tetrahydrofuran (10 mL) and methanol (5.0 mL) was added 1N sodium hydroxide (2.0 mL, 2.0 mmol) at room temperature. The mixture was stirred at room temperature for 3 days. To the reaction mixture was added 1N hydrogen chloride (2.0 mL, 2.0 mmol) at room temperature and the mixture was concentrated in vacuo. To the residue was added N,N-dimethylformamide (10 mL) and to the mixture were added N,O-dimethylhydroxylamine hydrochloride (81 mg, 0.83 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (159 mg, 0.83 mmol), 1-hydroxybenzotriazole monohydrate (127 mg, 0.83 mmol) and triethylamine (0.29 mL, 2.08 mmol). The mixture was stirred at room temperature for 24 hr. 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 to give the title compound (148.6 mg, 0.30 mmol, 72%) as a pale yellow amorphous.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additionTo the residue was added N,N-dimethylformamide (10 mL)
  3. stirringThe mixture was stirred at room temperature for 24 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel eluting with a 25-75% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-360b4af4e71641b4bc0df50d52545e2b
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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