Diisopropylethylamine → HCID 59902279, compound

HRID 2230707Notes

Reaction equation

HRID 2230707 reaction equation
I.I.[N:3]1([C:10]2[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:13]3[CH:20]=[CH:21][CH:22]=[CH:23][C:12]=3[N:11]=2)[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:36]=[N:35][N:34]=[N:33]2)=[CH:28][C:27]=1[C:37]([N:39]1[CH2:43][CH2:42][C@:41]([CH2:50][CH2:51]OS(C)(=O)=O)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:40]1)=[O:38].C(N(C(C)C)CC)(C)C>C(#N)C>[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:36]=[N:35][N:34]=[N:33]2)=[CH:28][C:27]=1[C:37]([N:39]1[CH2:43][CH2:42][C@:41]([CH2:50][CH2:51][N:6]2[CH2:7][CH2:8][CH2:9][N:3]([C:10]3[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:13]4[CH:20]=[CH:21][CH:22]=[CH:23][C:12]=4[N:11]=3)[CH2:4][CH2:5]2)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:40]1)=[O:38]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 18464587HCID 18464587, compoundHCID 86583904HCID 86583904, compound

Product 1

HCID 59902279HCID 59902279, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Heat a mixture of 2-[1,4]diazepan-1-yl-1-pentyl-1H-benzoimidazole dihydroiodide (0.83 g, 1.53 mmol), methanesulfonic acid 2-{(S)-1-[1-(2-methoxy-5-tetrazol-1-yl-phenyl)-methanoyl]-3-phenyl-pyrrolidin-3-yl}-ethyl ester (0.713 g, 1.51 mmol, example 47.2), diisopropylethylamine (1 mL, 5.74 mmol) and acetonitrile (15 mL) at 90° C. for 72 hours. Concentrate to dryness and dissolve the residue in dichloromethane. Wash the dichloromethane phase with NaHCO3 (10%, 10 mL) and brine (four 10 mL portions), dry (Na2SO4) the organic phase, filter and evaporate. Purify the residue by silica gel chromatography (3.5×35 cm) eluting with 95:5:0.05 dichloromethane:methanol:30% ammonium hydroxide solution. Concentrate the desired fractions to afford 0.19 g of the title compound, Rf=0.80 (silica gel, 90:10:0.1 dichloromethane:methanol:30% ammonium hydroxide solution). The product may be converted to the dihydrochloride by methods as are well known in the art.

Workup

  1. temperatureHeat
  2. concentrationConcentrate to dryness
  3. dissolutiondissolve the residue in dichloromethane
  4. washWash the dichloromethane phase with NaHCO3 (10%, 10 mL) and brine (four 10 mL portions)
  5. dry with materialdry (Na2SO4) the organic phase
  6. filtrationfilter
  7. customevaporate
  8. customPurify the residue by silica gel chromatography (3.5×35 cm)
  9. washeluting with 95:5:0.05 dichloromethane
  10. concentrationConcentrate the desired fractions

Sources & evidence

ORD record
ord-df212459ad124dbfbe36e527a04678ea
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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