Diiodomethane → 9-Chloro-6-[1-(cyclopropyloxy)-2,2,2-trifluoroethyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1399203Notes

Reaction equation

HRID 1399203 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]([OH:28])[C:24]([F:27])([F:26])[F:25])=[CH:4][CH:3]=1.C(OC=C)(=O)C.C(=O)([O-])[O-].[Na+].[Na+].C([Zn]CC)C.CCC[CH2:49][CH2:50][CH3:51].ICI>ClC1C=CC=CC=1Cl.C(OCC)(=O)C>[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]([O:28][CH:49]2[CH2:50][CH2:51]2)[C:24]([F:25])([F:26])[F:27])=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 6346DiiodomethaneHCID 7904Vinyl AcetateHCID 8058HexaneHCID 10340Sodium CarbonateHCID 577861691-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanolHCID 178418750HCID 178418750, compound

Product 1

HCID 577857809-Chloro-6-[1-(cyclopropyloxy)-2,2,2-trifluoroethyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 37%

Reagents, catalysts & solvents 2

HCID 72391,2-DichlorobenzeneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanol (135 mg, 0.300 mmol), vinyl acetate (277 μL, 3.00 mmol), di-μ-chlorobis[(η-cycloocta-1,5-diene)iridium (I)] (50.4 mg, 0.0750 mmol) and sodium carbonate (19.1, mg, 0.180 mmol) in o-dichlorobenzene (3.0 mL) was stirred for 27 h at 100° C. The reaction mixture was purified by flash column chromatography on silica gel eluting with a 25% ethyl acetate/n-hexane. The obtained compound was dissolved in dichloromethane (1.6 mL). A solution of diethyl zinc in hexane (1.0 M, 818 μL, 0.818 mmol) and diiodomethane (132 μL, 1.64 mmol) was added at 0° C. After being stirred for 4 h at room temperature, the reaction mixture was diluted with ethyl acetate, quenched with aqueous ammonium chloride, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on NH silica gel eluting with a 0-12% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (62.9 mg, 0.110 mmol, 37%). Analytically pure material was obtained by recrystallization from ethyl acetate/hexane.

Workup

  1. customThe reaction mixture was purified by flash column chromatography on silica gel eluting with a 25% ethyl acetate/n-hexane
  2. dissolutionThe obtained compound was dissolved in dichloromethane (1.6 mL)
  3. customquenched with aqueous ammonium chloride
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on NH silica gel eluting with a 0-12% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-5d1dec75a9874d13a474fbb4823f6c63
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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