Acetic Acid → HCID 49869632, compound

HRID 474932Notes

Reaction equation

HRID 474932 reaction equation
C[C:2](O)=[O:3].[F:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][N:17]([C:20]3[CH:21]=[CH:22][C:23]4[C:24]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29][C:25]=5[NH:26][C:27]=4[CH:28]=3)[C:16](=[O:34])[CH:15]=2)=[N:10][CH:11]=1.[CH2:35]([Cl:37])[Cl:36].[CH3:38][C:39]([CH3:41])=O>CC(C)=O>[CH2:35]([Cl:37])[Cl:36].[CH3:2][OH:3].[NH4+:10].[OH-:13].[F:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][N:17]([C:20]3[CH:21]=[CH:22][C:23]4[C:24]5[CH2:33][CH2:32][N:31]([CH:39]([CH3:41])[CH3:38])[CH2:30][CH2:29][C:25]=5[NH:26][C:27]=4[CH:28]=3)[C:16](=[O:34])[CH:15]=2)=[N:10][CH:11]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 21584124Propan-2-one--dichloromethane (1/1)HCID 49868941HCID 49868941, compound

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 49869632HCID 49869632, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

AcOH (0.42 mL) and picoline borane complex (51 mg, 0.47 mmol) were added to 4-((5-fluoropyridin-2-yl)methoxy)-1-(1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)-pyridin-2(1H)-one (69 mg, 0.16 mmol) suspended in 1:1 CH2Cl2/acetone (4.8 mL), and the resulting suspension was heated at reflux for 68 h. Additional acetone (1.0 mL) and picoline borane complex (20 mg, 19 mmol) were added, and the resulting suspension heated at reflux for 68 h. The reaction was cooled and concentrated to dryness under reduced pressure. 1 N HCl (10 ml) was added, and the suspension stirred at ambient temperature for 2 h. The mixture was made basic with 1 N NaOH and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. Preparative TLC (Analtech, 20×20 cm, 1000 microns, 80:18:2 CH2Cl2/MeOH/NH4OH) provided the title compound (31 mg, 43%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 10.86 (s, 1H), 8.61 (d, J=2.5 Hz, 1H), 7.82-7.81 (m, 1H), 7.66-7.63 (m, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.40 (d, J=8.5 Hz, 1H), 7.14 (s, 1H), 6.82 (d, J=7.0 Hz, 1H), 6.09 (dd, J=7.5, 3.0 Hz, 1H), 5.95 (d, J=3.0 Hz, 1H), 5.20 (s, 2H), 3.02-2.98 (m, 1H), 2.86-2.85 (m, 2H), 2.76 (m, 6H), 1.02 (d, J=6.5 Hz, 6H); ESI MS m/z 447 [M+H]+.

Workup

  1. temperaturethe resulting suspension was heated
  2. temperatureat reflux for 68 h
  3. temperaturethe resulting suspension heated
  4. temperatureat reflux for 68 h
  5. temperatureThe reaction was cooled
  6. concentrationconcentrated to dryness under reduced pressure
  7. addition1 N HCl (10 ml) was added
  8. extractionextracted with CH2Cl2 (3×20 mL)
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-c2c5768ddd514b599b9a83d228277530
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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