Hydroxylamine → HCID 178426453, compound

HRID 61487Notes

Reaction equation

HRID 61487 reaction equation
Cl.[NH2:2][OH:3].C[O-].[Na+].[C:7](/[N:9]=[C:10](\[N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1)/[N:11]1[CH2:16][CH2:15][C@H:14]([C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=3[CH3:33])[CH2:21][CH2:20]2)=[O:18])[C@@H:13]([C:34](OC)=[O:35])[CH2:12]1)#[N:8].NO>CO>[C:7](/[N:9]=[C:10](\[N:38]1[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]1)/[N:11]1[CH2:16][CH2:15][C@H:14]([C:17]([N:19]2[CH2:20][CH2:21][N:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=3[CH3:33])[CH2:23][CH2:24]2)=[O:18])[C@@H:13]([C:34]([NH:2][OH:3])=[O:35])[CH2:12]1)#[N:8]

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 178501356HCID 178501356, compound

Product 1

HCID 178426453HCID 178426453, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent5×

Conditions

Temperature
55 °C

Procedure

To a stirred suspension of hydroxylamine hydrochloride (1.56573 g, 0.0223062 mol) in anhydrous methanol (6.0 mL) at rt was added 4.37 M of sodium methoxide in methanol (7.64 mL). The reaction mixture was heated at 55° C. for 5 min, cooled to rt, then to 0° C. Filtration afforded a clear solution assumed to be ca. 1.50 M in methanol. To a stirred solution of methyl(3R,4S)-1-[(E)-(cyanoimino)(piperidin-1-yl)methyl]-4-[4-(4-cyano-2-methylphenyl)piperazin-1-yl]carbonylpiperidine-3-carboxylate (53.30 mg, 0.0001054 mol) in anhydrous methanol (1.110 mL, 0.02740 mol) at rt was added the above 1.50 M of hydroxylamine in methanol (1.40 mL). The reaction mixture was stirred at rt for 2 h. LCMS showed the reaction was done. The reaction was quenched with saturated aqueous NH4Cl, extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC with 5-95% MeCN/H2O to give the product. MS (ESI): (M+H)+=507.

Workup

  1. temperaturecooled to rt
  2. customto 0° C
  3. filtrationFiltration
  4. customafforded a clear solution
  5. customThe reaction was quenched with saturated aqueous NH4Cl
  6. extractionextracted with EtOAc (2×)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by reverse phase HPLC with 5-95% MeCN/H2O
  12. customto give the product

Sources & evidence

ORD record
ord-06c6610729224d2195a88b09188a18f4
Source dataset
uspto-grants-2016_09
Patent number
US09440958B2

Reaction notes

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