Triethylamine → HCID 59902277, compound

HRID 2230739Notes

Reaction equation

HRID 2230739 reaction equation
I.I.[N:3]1([C:10]2[N:14]([CH:15]=[CH2:16])[C:13]3[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=3[N:11]=2)[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:21][O:22][C:23]1[CH:48]=[CH:47][C:46]([N:49]2[CH:53]=[N:52][N:51]=[N:50]2)=[CH:45][C:24]=1[C:25]([N:27]1[CH2:31][CH2:30][C:29]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([CH2:32][CH2:33]OS(C)(=O)=O)[CH2:28]1)=[O:26].C(N(CC)CC)C>C(#N)C>[CH3:21][O:22][C:23]1[CH:48]=[CH:47][C:46]([N:49]2[CH:53]=[N:52][N:51]=[N:50]2)=[CH:45][C:24]=1[C:25]([N:27]1[CH2:31][CH2:30][C@@:29]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([CH2:32][CH2:33][N:6]2[CH2:7][CH2:8][CH2:9][N:3]([C:10]3[N:14]([CH:15]=[CH2:16])[C:13]4[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=4[N:11]=3)[CH2:4][CH2:5]2)[CH2:28]1)=[O:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 184648112-methoxy-5-(1H-tetrazol-1-yl)benzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)-pyrrolidineHCID 18465001HCID 18465001, compound

Product 1

HCID 59902277HCID 59902277, compoundYield 21.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Reflux a stirred solution of 2-[1,4]diazepan-1-yl-1-vinyl-1H-benzoimidazole dihydroiodide (0.70 g, 1.40 mmol), 1-(2-methoxy-5-(1H-tetrazol-1-yl)benzoyl-3-phenyl-3-(2-methanesulfonyloxyethyl)-pyrrolidine (0.61 g, 1.3 mmol, example 47.2), triethylamine (4.48 mmol) and acetonitrile (18 mL) under argon for 48 hours. Cool and concentrate in vacuo. Thin layer analysis (silica gel, 10% methanol/0.1% ammonium hydroxide solution in acetonitrile) indicates a mixture with a major component Rf=0.40. Dilute with dichloromethane (150 mL), wash the organic phase with NaHCO3 solution (50 mL), dry (Na2SO4) the organic phase, filter and evaporate in vacuo. Purify the residue by flash chromatography (silica gel, 7×15 cm) eluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane, concentrate the appropriate fractions to afford a tan solid. Purify the solid (in three separate injections of 110 mg, 250 mg and 250 mg) by reverse phase chromatography (PrepPak 40×100 mm μBondapak C18, 10 μm, 125 A°, Waters 037684, flow rate 35 mL/minute using the following gradients: 5 minutes with 10% acetonitrile/90% water with 0.1% trifluoroacetic acid, increase over 30 minutes to 50/50 water/acetonitrile, hold 5 minutes at 50/50 water/acetonitrile, increase over 5 minutes to 100% acetonitrile, hold 15 minutes at 100% acetonitrile). Combine the desired fractions to afford 0.17 g of the title compound.

Workup

  1. temperatureCool
  2. concentrationconcentrate in vacuo
  3. additionDilute with dichloromethane (150 mL)
  4. washwash the organic phase with NaHCO3 solution (50 mL)
  5. dry with materialdry (Na2SO4) the organic phase
  6. filtrationfilter
  7. customevaporate in vacuo
  8. customPurify the residue by flash chromatography (silica gel, 7×15 cm)
  9. washeluting with 10% methanol/0.1% ammonium hydroxide solution in dichloromethane
  10. concentrationconcentrate the appropriate fractions
  11. customto afford a tan solid
  12. customPurify
  13. customthe solid (in three separate injections of 110 mg, 250 mg and 250 mg) by reverse phase chromatography (PrepPak 40×100 mm μBondapak C18, 10 μm, 125 A°, Waters 037684, flow rate 35 mL/minute
  14. temperature5 minutes with 10% acetonitrile/90% water with 0.1% trifluoroacetic acid, increase over 30 minutes to 50/50 water/acetonitrile
  15. temperatureincrease over 5 minutes to 100% acetonitrile
  16. waithold 15 minutes at 100% acetonitrile

Sources & evidence

ORD record
ord-da3bbd44fd3d47628cbc59284e0fc654
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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