Pyridine → HCID 86624160, compound

HRID 1191112Notes

Reaction equation

HRID 1191112 reaction equation
Cl.[NH2:2][OH:3].N1C=CC=CC=1.[Cl:10][C:11]1[CH:27]=[CH:26][C:14]2[CH2:15][CH2:16][N:17]([C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH2:18][CH2:19][C:13]=2[C:12]=1[NH:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36](=O)[CH2:37][CH:38]([CH3:40])[CH3:39])=[CH:32][CH:31]=1>C(O)C>[Cl:10][C:11]1[CH:27]=[CH:26][C:14]2[CH2:15][CH2:16][N:17]([C:20](=[O:25])[C:21]([F:23])([F:24])[F:22])[CH2:18][CH2:19][C:13]=2[C:12]=1[NH:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36](=[N:2][OH:3])[CH2:37][CH:38]([CH3:40])[CH3:39])=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 58495679HCID 58495679, compound

Product 1

HCID 86624160HCID 86624160, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Add hydroxylamine hydrochloride (6.3 mg, 0.091 mmol) and pyridine (15 uL, 0.182 mmol) to a solution of 7-chloro-6-[4-(3-methyl-butyryl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (42 mg, 0.091 mmol) in ethanol (1 mL). Heat the mixture to reflux for 18 h. Remove the solvent in vacuo and partition the residue between DCM and 0.1N aqueous HCl. Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (95:5 to 1:1 gradient over 30 min). Concentrate in vacuo to obtain 7-chloro-6-[4-(1-hydroxyimino-3-methyl-butyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an off-white solid (19.1 mg, 44%). MS (ES+) m/z: 482 (M+H)+.

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux for 18 h
  3. customRemove the solvent in vacuo
  4. custompartition the residue between DCM and 0.1N aqueous HCl
  5. dry with materialDry the organic phase over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel eluting with hexane/EtOAc (95:5 to 1:1 gradient over 30 min)
  9. concentrationConcentrate in vacuo

Sources & evidence

ORD record
ord-0eb6e92325b542288ee7b0d4d4b0a55c
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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