Triethylamine → Methyl 9-chloro-1-(2,6-dibromo-4-methoxyphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

HRID 1628915Notes

Reaction equation

HRID 1628915 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:12][CH2:13][CH2:14][CH2:15]O)[C:3]=1[NH:17][C:18](=S)[NH:19][C:20]1[C:25]([Br:26])=[CH:24][C:23]([O:27][CH3:28])=[CH:22][C:21]=1[Br:29].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(OCC)(=O)C.CN(C)C=O>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]2[C:3]=1[N:17]=[C:18]1[N:19]([C:20]3[C:21]([Br:29])=[CH:22][C:23]([O:27][CH3:28])=[CH:24][C:25]=3[Br:26])[CH2:15][CH2:14][CH2:13][N:12]21

Participants

9

Reactant 5

HCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86632933Methyl 4-chloro-3-{[(2,6-dibromo-4-methoxyphenyl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoate

Product 1

HCID 57786326Methyl 9-chloro-1-(2,6-dibromo-4-methoxyphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 91.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 4-chloro-3-{[(2,6-dibromo-4-methoxyphenyl)carbamothioyl]amino}-2-[(3-hydroxypropyl)amino]benzoate (560 mg, 0.963 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (203 mg, 1.06 mmol) and triethylamine (0.148 mL, 1.06 mmol) in tetrahydrofuran (10 mL) was stirred at 50° C. for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. To a mixture of residue and triethylamine (0.671 mL, 4.81 mmol) in tetrahydrofuran (10 mL) was added methanesulfonyl chloride (0.304 mL, 3.85 mmol) at 0° C. The resultant mixture was stirred at room temperature for 1 h and concentrated in vacuo. After N,N-dimethylformamide (10 mL) and potassium carbonate (1.33 g, 9.62 mmol) were added to the residue, the resultant mixture was stirred at 80° C. for 4 h, diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 30-60% ethyl acetate/n-hexane gradient mixture to give the title compound as a brown solid (466 mg, 0.881 mmol, 91%).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. concentrationconcentrated in vacuo
  6. washwashed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash column chromatography on silica gel eluting with a 30-60% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-ac9195d8e11342f1a32f9b067980bf18
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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