2-Chloro-5-(chloromethyl)thiophene → 8-Chloro-1-(3-{1-[(5-chloro-2-thienyl)methyl]-1H-pyrazol-4-yl}propyl)-3-pentyl-3,7-dihydro-1H-purine-2,6-dione

HRID 1097711Notes

Reaction equation

HRID 1097711 reaction equation
[Cl:1][C:2]1[N:10](CC=C)[C:9]2[C:8](=[O:14])[N:7]([CH2:15][CH2:16][CH2:17][C:18]3[CH:19]=[N:20][NH:21][CH:22]=3)[C:6](=[O:23])[N:5]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:4]=2[N:3]=1.CC(C)([O-])C.[K+].[Cl:35][C:36]1[S:37][C:38]([CH2:41]Cl)=[CH:39][CH:40]=1>C1COCC1>[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:14])[N:7]([CH2:15][CH2:16][CH2:17][C:18]3[CH:22]=[N:21][N:20]([CH2:41][C:38]4[S:37][C:36]([Cl:35])=[CH:40][CH:39]=4)[CH:19]=3)[C:6](=[O:23])[N:5]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 5830792-Chloro-5-(chloromethyl)thiopheneHCID 23665647Potassium tert-butoxideHCID 593958038-Chloro-3-pentyl-7-(2-propen-1-yl)-1-[3-(1H-pyrazol-4-yl)propyl]-3,7-dihydro-1H-purine-2,6-dione

Product 1

HCID 593955318-Chloro-1-(3-{1-[(5-chloro-2-thienyl)methyl]-1H-pyrazol-4-yl}propyl)-3-pentyl-3,7-dihydro-1H-purine-2,6-dioneYield 6.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 8-chloro-3-pentyl-7-(2-propen-1-yl)-1-[3-(1H-pyrazol-4-yl)propyl]-3,7-dihydro-1H-purine-2,6-dione (61 mg, 0.15 mmol) in dry THF (1 ml) at −78° C., under nitrogen, was added potassium t-butoxide (1M in THF, 0.15 ml), followed by 2-chloro-5-(chloromethyl)thiophene (25 mg, 0.15 mmol). Stirring was continued at −78° C. for 15 min, then at room temperature for 1 h and finally at 60° C. for 18 h. The solution was degassed and morpholine (0.13 ml) and tetrakis(triphenylphosphine)palladium(0) (35 mg) added and stirring continued for 6 h. Further quantities (0.2 ml morpholine, 50 mg Pd(PPh3)4) were added and stirring continued overnight. Worked up by partition between EtOAc and 2M HCl, the organic phase evaporated and purified by the standard aminopropyl SPE procedure followed by MDAP yielding title compound as a white solid (5.1 mg).

Workup

  1. waitat room temperature for 1 h
  2. waitfinally at 60° C. for 18 h
  3. customThe solution was degassed
  4. additionmorpholine (0.13 ml) and tetrakis(triphenylphosphine)palladium(0) (35 mg) added
  5. stirringstirring
  6. waitcontinued for 6 h
  7. additionFurther quantities (0.2 ml morpholine, 50 mg Pd(PPh3)4) were added
  8. stirringstirring continued overnight
  9. customby partition between EtOAc and 2M HCl
  10. customthe organic phase evaporated
  11. custompurified by the standard aminopropyl SPE procedure

Sources & evidence

ORD record
ord-788bd5add134417d8de9c31a0c611e1a
Source dataset
uspto-grants-2012_03
Patent number
US08143264B2

Reaction notes

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