Water → HCID 145784130, compound

HRID 335612Notes

Reaction equation

HRID 335612 reaction equation
[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[C:20]([C:22]#[N:23])[CH:19]=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.Cl.[NH2:25][OH:26].C(=O)([O-])[O-].[K+].[K+].O>C(O)C>[ClH:1].[ClH:1].[NH2:23]/[C:22](=[N:25]\[OH:26])/[C:20]1[CH:19]=[CH:18][C:16]2[CH:17]=[C:13]([C:11]([NH:10][C@@H:4]3[CH:5]4[CH2:6][CH2:7][N:2]([CH2:9][CH2:8]4)[CH2:3]3)=[O:12])[S:14][C:15]=2[CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 67314100HCID 67314100, compound

Product 1

HCID 145784130HCID 145784130, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

800 mg (2.0 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-cyano-1-benzo-thiophene-2-carboxamide hydrochloride, 278.1 mg (4.0 mmol) of hydroxylamine hydrochloride and 829.5 mg (6.0 mmol) of potassium carbonate in 8 ml of an 8:1 mixture of water and ethanol are heated at 80° C. for 3 h. The mixture is purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol/25% ammonia 100:20:4). The product fractions are combined and concentrated, methanol and 4M HCl in dioxane are added and the mixture is then again concentrated and dried under high vacuum. 447.3 mg (53.6% of theory) of the title compound are obtained.

Workup

  1. customThe mixture is purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol/25% ammonia 100:20:4)
  2. concentrationconcentrated
  3. additionmethanol and 4M HCl in dioxane are added
  4. concentrationthe mixture is then again concentrated
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-920dcf50bb324b0087d82a4a9e20906c
Source dataset
uspto-grants-2014_11
Patent number
US08884017B2

Reaction notes

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