Potassium Carbonate → Methyl 9-chloro-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

HRID 1628754Notes

Reaction equation

HRID 1628754 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[C:15]2[N:14]=[C:13]([NH:16][C:17]3[C:18]([CH3:26])=[N:19][C:20]([O:24][CH3:25])=[N:21][C:22]=3[CH3:23])[N:12]([CH2:27][CH2:28][CH2:29]O)[C:11]=2[C:10]([C:31]([O:33][CH3:34])=[O:32])=[CH:9][CH:8]=1.S([O-])(=O)(=O)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C)C=O.[Cl-].[NH4+].C(N(CC)CC)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([C:31]([O:33][CH3:34])=[O:32])=[C:11]2[C:15]=1[N:14]=[C:13]1[N:16]([C:17]3[C:22]([CH3:23])=[N:21][C:20]([O:24][CH3:25])=[N:19][C:18]=3[CH3:26])[CH2:29][CH2:28][CH2:27][N:12]21

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 68760563Methyl 4-chloro1-(3-hydroxypropyl)-2-[(2-methoxy-4,6-dimethylpyrimidin-5-yl)amino]-1H-benzimidazole-7-carboxylate

Product 1

HCID 57786073Methyl 9-chloro-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateYield 76.5%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Methanesulfonyl chloride (4.57 mL, 57.8 mmol) was added to a stirred solution of methyl 4-chloro-1-(3-hydroxypropyl)-2-[(2-methoxy-4,6-dimethylpyrimidin-5-yl)amino]-1H-benzimidazole-7-carboxylate (Reference example 127, 11.9 g, 28.9 mmol) and triethylamine (12.1 mL) in tetrahydrofuran (400 mL) at 0° C. The mixture was stirred at 0° C. for 50 min, and concentrated in vacuo. A mixture of the resulting mesylate and potassium carbonate (12.0 g, 86.8 mmol) in N,N-dimethylformamide (200 mL) was stirred at 80° C. for 2 hr. The mixture was diluted with aqueous saturated ammonium chloride, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound as a pale yellow solid (8.88 g, 22.1 mmol, 76% in 2 steps).

Workup

  1. concentrationconcentrated in vacuo
  2. stirringwas stirred at 80° C. for 2 hr
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a 50-100% ethyl acetate/n-hexane gradient mixture
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-5b60d29df93f47978f18a61b2ea999a8
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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