Hydrochloric Acid → HCID 86627419, compound

HRID 1988794Notes

Reaction equation

HRID 1988794 reaction equation
C1C2C3=CC4[CH:14]=[CH:15][C:16](C(O)=O)=[CH:17][C:18]=4[N:9]3CC=CC=2C=CC=1.[ClH:22].[C:23]([N:30]1[CH:34]=[CH:33][N:32]=[CH:31]1)(N1C=CN=C1)=[O:24].CN1CCNCC1.[CH2:42]1CCN2[C:45](=NCCC2)[CH2:44][CH2:43]1>C1COCC1.CO.[OH-].[Na+].C1COCC1>[Cl:22][C:18]1[C:17]([C:23]([N:30]2[CH:34]3[CH2:45][CH2:44][CH:43]2[CH2:42][N:32]([CH3:31])[CH2:33]3)=[O:24])=[CH:16][CH:15]=[CH:14][N:9]=1

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 531671-MethylpiperazineHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 666396797H-indolo[2,1-a][2]benzazepine-10-carboxylic acid2×

Product 1

HCID 86627419HCID 86627419, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6-[3-[(4-methyl-1-piperazinyl)carbonyl]-2-pyridinyl]-, 1,1-dimethylethyl ester. 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[3-(ethoxycarbonyl)-2-pyridinyl]-3-methoxy-, 1,1-dimethylethyl ester (159 mg, 0.269 mmol) was dissolved in a 1:1 solution of THF/MeOH (10 mL) and 1M NaOH (5 mL) was added. The resulting mixture was stirred at 22° C. for 16 hr. 1M HCl (25 mL) was added and the aqueous layer was extracted with CHCl3 (2×25 mL). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a white solid. This solid was redissolved in THF (1 mL) and carbonyldiimidazole (60 mg, 0.370 mmol) was added. The resulting solution was stirred at 22° C. under a nitrogen atmosphere for 1.5 hrs then heated to reflux for 1 hr. Upon cooling to room temperature under a nitrogen atmosphere, 1-methylpiperazine (62 mg, 0.615 mmol) and DBU (46 mg, 0.370 mmol) were added and the reaction stirred at 22° C. for 18 hr. 1M HCl (10 mL) was added and the aqueous layer was extracted with CHCl3 (2×25 mL). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the title compound (165 mg, 95%) as a yellow paste. MS m/z 647 (MH+).

Workup

  1. additionwas added
  2. extractionthe aqueous layer was extracted with CHCl3 (2×25 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a white solid
  7. stirringThe resulting solution was stirred at 22° C. under a nitrogen atmosphere for 1.5 hrs
  8. temperaturethen heated
  9. temperatureto reflux for 1 hr
  10. temperatureUpon cooling to room temperature under a nitrogen atmosphere
  11. stirringthe reaction stirred at 22° C. for 18 hr
  12. extractionthe aqueous layer was extracted with CHCl3 (2×25 mL)
  13. dry with materialThe organic phase was dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2bfbad8b371d4f698459da998abd8b6a
Source dataset
uspto-grants-2010_01
Patent number
US07642251B2

Reaction notes

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