Chloride → 6-Amino-2-(cyclohexyloxy)-9-[4-(1-piperidinyl)butyl]-7,9-dihydro-8H-purin-8-one

HRID 590505Notes

Reaction equation

HRID 590505 reaction equation
[I-].[Na+].Cl[CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:16]([O:17]C)=[N:15][C:14]2[C:9]1=[N:10][C:11]([O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)=[N:12][C:13]=2[NH2:19].C(N(CC)C(C)C)(C)C.[NH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.[Cl-]>CN(C=O)C>[NH2:19][C:13]1[N:12]=[C:11]([O:20][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]2)[N:10]=[C:9]2[C:14]=1[NH:15][C:16](=[O:17])[N:8]2[CH2:7][CH2:6][CH2:5][CH2:4][N:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1

Participants

7

Reactant 5

HCID 312ChlorideHCID 5238Sodium IodideHCID 8082Piperidine2×HCID 81531DiisopropylethylamineHCID 592526519-(4-chlorobutyl)-2-(cyclohexyloxy)-8-(methyloxy)-9H-purin-6-amine

Product 1

HCID 592526316-Amino-2-(cyclohexyloxy)-9-[4-(1-piperidinyl)butyl]-7,9-dihydro-8H-purin-8-oneYield 14.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium iodide (0.006 g, 0.04 mmol) was added to a stirred mixture of 9-(4-chlorobutyl)-2-(cyclohexyloxy)-8-(methyloxy)-9H-purin-6-amine (0.103 g, 0.303 mmol), N,N-diisopropylethylamine (0.105 ml, 0.079 g, 0.609 mmol) and piperidine (0.120 ml, 0.103 g, 1.215 mmol) in DMF (1.5 ml). The resultant mixture was heated at 80° C. for 20 hours when LCMS showed the formation of two products, one corresponding to displacement of the chloride by piperidine and the second corresponding to concomitant hydrolysis of the 8-methoxy moiety. The reaction mixture was partitioned between dichloromethane (6 ml) and water (6 ml) and the phases separated using a hydrophobic frit. The solvent was removed from the organic phase under a stream of nitrogen in a blow-down unit and the residue was dissolved in 1:1 MeOH:DMSO (2 ml) and separated by mass directed autopreparation (Method A) to afford the title compound as a white solid (16.6 mg).

Workup

  1. customThe reaction mixture was partitioned between dichloromethane (6 ml) and water (6 ml)
  2. customthe phases separated
  3. customThe solvent was removed from the organic phase under a stream of nitrogen in a blow-down unit
  4. dissolutionthe residue was dissolved in 1:1 MeOH
  5. customDMSO (2 ml) and separated by mass

Sources & evidence

ORD record
ord-2a137e903e404a94ac74636f9f9e1c6a
Source dataset
uspto-grants-2016_01
Patent number
US09233962B2

Reaction notes

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