Pyridine → HCID 69521911, compound

HRID 856498Notes

Reaction equation

HRID 856498 reaction equation
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([CH2:38]O)=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:40]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.S(Cl)(Cl)=O.[CH3:51][N:52]1[C:56]([SH:57])=[N:55][N:54]=[N:53]1>C1COCC1.O.C(N(CC)CC)C>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([CH2:38][S:57][C:56]5[N:52]([CH3:51])[N:53]=[N:54][N:55]=5)=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:40]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 69522440HCID 69522440, compoundHCID 178482017HCID 178482017, compound

Product 1

HCID 69521911HCID 69521911, compoundYield 73.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

In THF (12 ml) was dissolved 7-[4-(2-butoxyethoxy)phenyl]-N-[4-(hydroxymethyl)phenyl]-1-isobutyl-2,3-dihydro-1-benzazepine-4-carboxamide (0.60 g), and pyridine (3 droplets) and thionyl chloride (0.16 ml) were added to the mixture. The solution was stirred at room temperature for 1 hour, and added dropwise to a solution of 1-methyl-1,2,3,4-tetrazole-5-thiol (154 mg) and triethylamine (1.23 ml) in THF (12 ml) at 0° C. The mixture was stirred at room temperature for 2 hours, and stirred for 16 hours at 50° C. After allowing to be cooled to room temperature, the reaction solution was added to water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[(1-methyl-1,2,3,4-tetrazol-5-yl)sulfanyl]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 245) (520 mg).

Workup

  1. additionwere added to the mixture
  2. stirringThe mixture was stirred at room temperature for 2 hours
  3. stirringstirred for 16 hours at 50° C
  4. temperatureto be cooled to room temperature
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was removed under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-4570c3746b1540f9870ae82fd619554f
Source dataset
uspto-grants-2007_08
Patent number
US07262185B2

Reaction notes

Loading…