p-Toluenesulfonic acid → HCID 12001404, compound

HRID 503215Notes

Reaction equation

HRID 503215 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][O:8][CH2:9][C:10]2[CH:11]=[C:12]([NH:16][C:17]3[C:18]([NH2:27])=[CH:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[CH:13]=[CH:14][CH:15]=2)=[N:5][CH:4]=[N:3]1.[CH:28](OCC)(OCC)OCC.C1(C)C=CC(S(O)(=O)=O)=CC=1.CC1C=CC2N(C3C=CC=C(COCC4N(C)N=CN=4)C=3)C=NC=2C=1.CC1C=C(N)C(NC2C=CC=C(COCC3N(C)N=CN=3)C=2)=CC=1.CN1C(COCC2C=C(N3C4C=CC(C(=O)C)=CC=4N=C3)C=CC=2)=NC=N1.NC1C=C(C(=O)C)C=CC=1NC1C=CC=C(COCC2N(C)N=CN=2)C=1>C1COCC1>[CH3:1][N:2]1[C:6]([CH2:7][O:8][CH2:9][C:10]2[CH:11]=[C:12]([N:16]3[C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:24])([F:26])[F:25])=[CH:19][C:18]=4[N:27]=[CH:28]3)[CH:13]=[CH:14][CH:15]=2)=[N:5][CH:4]=[N:3]1

Participants

9

Reactant 7

HCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformateHCID 12001406HCID 12001406, compoundHCID 12001407HCID 12001407, compoundHCID 68458392HCID 68458392, compoundHCID 68461917HCID 68461917, compoundHCID 86626711HCID 86626711, compound

Product 1

HCID 12001404HCID 12001404, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 20a in anhydrous THF (15 ml) was added triethyl orthoformate (0.75 ml, 4.4 mmol) and a catalytic amount of p-toluenesulphonic acid. The resultant mixture was stirred at reflux for 1 hour. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and methanol (9:1 v/v). Compound 21a (0.87 g) was precipitated as the hydro chloride by addition of etheral hydrogen chloride to the pure fractions. LC-ESI-HRMS of [M+H]+ shows 388.14 Da. Calc. 388.138519 Da, dev. 3.8 ppm The following compounds were prepared in analogy herewith: 1-[3-(2-Ethyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-5-trifluoromethyl-1H-benzoimidazole (21b) from compound 20b. Yield: 67%. LC-ESI-HRMS of [M+H]+ shows 402.1548 Da. Calc. 402.154169 Da, dev. 1.6 ppm 5-Methyl-1-[3-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazole (21c) from compound 20c. Yield: 7% (3 steps). LC-ESI-HRMS of [M+H]+ shows 334.1679 Da. Calc. 334.166785 Da, dev. 3.3 ppm 1-{1-[3-(2-Methyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-1H-benzoimidazol-5-yl}-ethanone (21d) from compound 20d. Yield: 53% isolated as the free base. Mp 121.4-123.6° C.

Workup

  1. temperatureat reflux for 1 hour
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by column chromatography on silica gel
  4. washeluting with a mixture of ethyl acetate and methanol (9:1 v/v)
  5. customCompound 21a (0.87 g) was precipitated as the hydro chloride by addition of etheral hydrogen chloride to the pure fractions
  6. custom3.8 ppm The following compounds were prepared in analogy herewith: 1-[3-(2-Ethyl-2H-[1,2,4]triazol-3-ylmethoxymethyl)-phenyl]-5-trifluoromethyl-1H-benzoimidazole (21b) from compound 20b
  7. customYield: 53% isolated as the free base

Sources & evidence

ORD record
ord-6085ad13aac940f3a8371d28c4d11657
Source dataset
uspto-grants-2010_08
Patent number
US07776900B2

Reaction notes

Loading…