Ammonia → HCID 86721350, compound

HRID 869522Notes

Reaction equation

HRID 869522 reaction equation
[C:1](/[C:3](=[C:5]1/[C:6]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:7]=2[O:8][CH2:9][C:10]2[CH:15]=[C:14]([CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([C:26]([OH:28])=O)[C:20]=4[N:19]=[C:18]3[CH2:29][CH2:30][CH3:31])[CH:13]=[CH:12][C:11]/1=2)/[CH3:4])#[N:2].C(N1C=CN=C1)([N:39]1C=CN=C1)=O.N.Cl>C1COCC1.O>[C:1](/[C:3](=[C:5]1/[C:6]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:7]=2[O:8][CH2:9][C:12]2[CH:13]=[C:14]([CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([C:26]([NH2:39])=[O:28])[C:20]=4[N:19]=[C:18]3[CH2:29][CH2:30][CH3:31])[CH:15]=[CH:10][C:11]/1=2)/[CH3:4])#[N:2]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 86721351HCID 86721351, compound

Product 1

HCID 86721350HCID 86721350, compoundYield 100.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

[step 5] (E)-1-{[11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl}-2-propyl-1H-benzo[d]imidazole-4-carboxylic acid (97 mg, 0.20 mmol) obtained in step 4 was dissolved in THF (1.0 mL), 1,1′-carbonyldiimidazole (130 mg, 0.80 mmol) was added, and the mixture was stirred at 50° C. for 4 hr. After cooling to room temperature, 25% aqueous ammonia solution (55 μL, 0.80 mmol) was added, and the mixture was stirred at room temperature for 17 hr. To the mixture were added 1 mol/L hydrochloric acid and water, and the mixture was extracted 3 times with chloroform. The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-93/7 v/v) to give the title compound (97 mg, 100%).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringthe mixture was stirred at room temperature for 17 hr
  3. extractionthe mixture was extracted 3 times with chloroform
  4. washThe combined organic layers were washed with saturated aqueous sodium hydrogen carbonate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-93/7 v/v)

Sources & evidence

ORD record
ord-19e52e086c3c4b8fbb071aaa6c33dcda
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

Loading…