Triethylamine → Methyl 1-(3-chloropropyl)-4-methoxy-2-[(2-methoxy-4,6-dimethylpyrimidin-5-yl)amino]-1H-benzimidazole-7-carboxylate

HRID 1398960Notes

Reaction equation

HRID 1398960 reaction equation
[NH2:1][C:2]1[C:3]([NH:14][CH2:15][CH2:16][CH2:17][Cl:18])=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([O:7][CH3:8])=[O:6].[N:19]([C:22]1[C:23]([CH3:31])=[N:24][C:25]([O:29][CH3:30])=[N:26][C:27]=1[CH3:28])=[C:20]=S.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>O1CCCC1.O>[Cl:18][CH2:17][CH2:16][CH2:15][N:14]1[C:3]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[C:11]([O:12][CH3:13])[C:2]=2[N:1]=[C:20]1[NH:19][C:22]1[C:27]([CH3:28])=[N:26][C:25]([O:29][CH3:30])=[N:24][C:23]=1[CH3:31]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 68737411Methyl 3-amino-2-[(3-chloropropyl)amino]-4-methoxybenzoateHCID 866328935-Isothiocyanato-2-methoxy-4,6-dimethylpyrimidine

Product 1

HCID 68771677Methyl 1-(3-chloropropyl)-4-methoxy-2-[(2-methoxy-4,6-dimethylpyrimidin-5-yl)amino]-1H-benzimidazole-7-carboxylateYield 66%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
40 °C

Procedure

A mixture of methyl 3-amino-2-[(3-chloropropyl)amino]-4-methoxybenzoate (965 mg, 3.55 mmol) and 5-isothiocyanato-2-methoxy-4,6-dimethylpyrimidine (1.04 g, 5.32 mmol) in tetrahydrofuran (15 mL) was stirred at 40° C. for 3 days. The solvent was removed in vacuo and the solid was collected by filtration, washed with diisopropyl ether. A mixture of the solid (1.589 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.72 g, 3.76 mmol) and triethylamine (0.52 mL, 3.73 mmol) in tetrahydrofuran (16 mL) was stirred at 50° C. for 3 hr. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (130 mg, 0.678 mmol) and triethylamine (0.095 mL, 0.682 mmol) were added to the reaction mixture at room temperature and the mixture was stirred at 50° C. for 1 hr. Water was added to the reaction mixture at room temperature and the mixture was extracted with a mixture of ethyl acetate, THF and N,N-dimethylformamide. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (878.9 mg, 2.03 mmol, 66%) as a pale red solid.

Workup

  1. customThe solvent was removed in vacuo
  2. filtrationthe solid was collected by filtration
  3. washwashed with diisopropyl ether
  4. stirringwas stirred at 50° C. for 3 hr
  5. stirringthe mixture was stirred at 50° C. for 1 hr
  6. extractionthe mixture was extracted with a mixture of ethyl acetate, THF and N,N-dimethylformamide
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3fd28d0b5f644bafbfb5cf095f0a1e62
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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