Sodium Iodide → HCID 9949709, compound

HRID 1744003Notes

Reaction equation

HRID 1744003 reaction equation
CC1NC(C)=CC=1[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[C:22]3[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=3[C:16]([OH:23])=[CH:15][CH:14]=2)[N:8]=1.Cl[CH:26]1C[CH2:30][CH2:29][CH2:28][C:27]1=O.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].Cl.CON.[CH2:45]=[N:46]O.CSC.B.C(=O)([O-])[O-].[Na+].[Na+].[F-].[Cs+].Cl.[NH2:61]O>CN(C)C=O.CO.O1CCCC1.C(O)C.C(N(CC)CC)C>[NH2:46][CH:45]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[O:23][C:16]1[C:17]2[CH2:18][CH2:19][CH2:20][CH2:21][C:22]=2[C:13]([C:9]2[N:8]=[C:7]([NH2:61])[CH:12]=[CH:11][CH:10]=2)=[CH:14][CH:15]=1

Participants

16

Reactant 10

HCID 5238Sodium IodideHCID 6350NitroneHCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 132032-ChlorocyclohexanoneHCID 25953Cesium fluorideHCID 443297Hydroxyamine hydrochlorideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 12423031(Dimethyl sulfide)trihydroboronHCID 135968514HCID 135968514, compound

Product 1

HCID 9949709HCID 9949709, compoundYield 89%

Reagents, catalysts & solvents 5

HCID 702EthanolSolvent2×HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Prepared as in Example 48, via the following four-step sequence: 2-(2,5-dimethylpyrrolyl)-6-[4-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl]-pyridine was first alkylated with 2-chlorocyclohexanone, using potassium carbonate as the base and a catalytic amount of sodium iodide, in dimethylformamide at 80° C. for 24 hours, in 92% yield. The resulting ketone was converted to the oxime methyl ether using O-methylhydroxylamine hydrochloride and triethylamine in methanol at reflux for 16 h in 81% yield. The oxime ether was then reduced to the amine using borane methyl sulfide in tetrahydrofuran at reflux for 2 days, followed by refluxing in ethanol with sodium carbonate and cesium fluoride for 16 hours, in 12% yield. The amine was then deblocked with hydroxylamine hydrochloride in refluxing aqueous ethanol to afford the desired final product in 89% yield as a tan solid after conversion to the hydrochloride salt.

Workup

  1. customPrepared as in Example 48
  2. temperatureat reflux for 16 h in 81% yield
  3. temperatureat reflux for 2 days

Sources & evidence

ORD record
ord-4edf3a17f5974a37a43b3d8bfcde1d6d
Source dataset
uspto-grants-2006_03
Patent number
US07012078B2

Reaction notes

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