Morpholine → 3-Butyl-8-chloro-1-[4-(5-phenyl-2H-tetrazol-2-yl)butyl]-3,7-dihydro-1H-purine-2,6-dione

HRID 1097707Notes

Reaction equation

HRID 1097707 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:18](=[O:19])[C:17]2[N:16](CC=C)[C:15]([Cl:23])=[N:14][C:13]=2[N:12]([CH2:24][CH2:25][CH2:26][CH3:27])[C:11]1=[O:28])(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+].[C:35]1([C:41]2[NH:45][N:44]=[N:43][N:42]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.N1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.CN(C=O)C>[CH2:24]([N:12]1[C:13]2[N:14]=[C:15]([Cl:23])[NH:16][C:17]=2[C:18](=[O:19])[N:10]([CH2:9][CH2:8][CH2:7][CH2:6][N:43]2[N:44]=[N:45][C:41]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[N:42]2)[C:11]1=[O:28])[CH2:25][CH2:26][CH3:27]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 594051074-[3-butyl-8-chloro-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purin-1-yl]butyl methanesulfonateHCID 178418369HCID 178418369, compound

Product 1

HCID 593957073-Butyl-8-chloro-1-[4-(5-phenyl-2H-tetrazol-2-yl)butyl]-3,7-dihydro-1H-purine-2,6-dioneYield 29%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-[3-butyl-8-chloro-2,6-dioxo-7-(2-propen-1-yl)-2,3,6,7-tetrahydro-1H-purin-1-yl]butyl methanesulfonate (50 mg, 0.12 mmol), Cs2CO3 (45 mg, 0.14 mmol) and DMF (3 ml) was treated with 5-phenyl-1H-tetrazole (20 mg, 0.14 mmol) and stirred for 60 h at 50° C. After cooling, the mixture was degassed by applying a vacuum and then nitrogen was introduced. Pd(PPh3)4 (20 mg, 0.017 mmol) was added and the mixture degassed once more. Morpholine (150 μl, 1.7 mmol) was added and the mixture was stirred under nitrogen for 18 h, then partitioned between 2M HCl (aq) and EtOAc. The organic layer was separated and the aqueous layer extracted again with EtOAc. The combined extracts were concentrated, giving a yellow residue. MeOH was added and then passed down an NH2-propyl column with the product eluting with 2% AcOH/MeOH. Further purification by MDAP gave the title compound as an off-white solid (15 mg, 29%).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was degassed
  3. additionnitrogen was introduced
  4. customthe mixture degassed once more
  5. stirringthe mixture was stirred under nitrogen for 18 h
  6. custompartitioned between 2M HCl (aq) and EtOAc
  7. customThe organic layer was separated
  8. extractionthe aqueous layer extracted again with EtOAc
  9. concentrationThe combined extracts were concentrated
  10. customgiving a yellow residue
  11. washeluting with 2% AcOH/MeOH
  12. customFurther purification by MDAP

Sources & evidence

ORD record
ord-be91b9f286f7448ba317d53d657223f7
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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