Pentane → 1H-Purine, 6-[[3-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]propyl]thio]-

HRID 2352434Notes

Reaction equation

HRID 2352434 reaction equation
CCCCC.[H-].[Na+].O.[SH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[NH:12][CH:13]=[N:14]2.Cl[CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][N:26]([CH:29]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH2:25][CH2:24]1>CN(C=O)C.CO.C(Cl)Cl>[F:43][C:40]1[CH:41]=[CH:42][C:37]([CH:29]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[N:26]2[CH2:25][CH2:24][N:23]([CH2:22][CH2:21][CH2:20][S:9][C:10]3[N:18]=[CH:17][N:16]=[C:15]4[C:11]=3[NH:12][CH:13]=[N:14]4)[CH2:28][CH2:27]2)=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 8003PentaneHCID 24758Sodium hydrideHCID 15670863HCID 15670863, compoundHCID 178527204HCID 178527204, compound

Product 1

HCID 103904161H-Purine, 6-[[3-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]propyl]thio]-Yield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

Pentane (10 mL) was added to sodium hydride (0.3 g, 6.3 mmol, 50% suspension in mineral oil), and the mixture was stirred under nitrogen. The pentane was decanted, anhydrous DMF (12 mL) was added and the suspension was cooled to 0° C. 6-Mercaptopurine monohydrate (0.93 g, 5.5 mmol) was added in small portions over a 15 min period. To the light beige, slightly hazy mixture was added, after an additional 10 min at 0° C., 1-(1-chloro-3-propanyl)-4-[bis(4-fluorphenyl)methyl]piperazine (2.0 g, 5.5 mmol) dissolved in anhydrous DMF (4mL) within 5 min. After addition was complete, the mixture was allowed to warm to room temperature and it was stirred under nitrogen for 4 days. The DMF was evaporated in vacuo (1 mm Hg) at 50° C. The residue was triturated in methylene chloride and the mixture was filtered through celite. The filtrate was washed with water (2×50 mL), dried (sodium sulfate), filtered, and evaporated in vacuo to give the crude product (2.79 g). Silica gel flash chromatography using 10% methanol/methylene chloride gave the desired product (1.18 g, 45%) mp 90°-93° C. 300 MHz 1H NMR (CDCl3) δ: 8.60 (s, 1H), 8.14 (s, 1H), 7.31 (m, 4H), 6.95 (m, 4H), 4.17 (s, 1H), 3.38 (m, 2H), 2.35-2.6 (m, 10H), 2.02 (m, 2H). DCI/MS (M+1) 481.

Workup

  1. customThe pentane was decanted
  2. additionanhydrous DMF (12 mL) was added
  3. additionTo the light beige, slightly hazy mixture was added, after an additional 10 min at 0° C.
  4. additionAfter addition
  5. temperatureto warm to room temperature
  6. stirringit was stirred under nitrogen for 4 days
  7. customThe DMF was evaporated in vacuo (1 mm Hg) at 50° C
  8. customThe residue was triturated in methylene chloride
  9. filtrationthe mixture was filtered through celite
  10. washThe filtrate was washed with water (2×50 mL)
  11. dry with materialdried (sodium sulfate)
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. customto give the crude product (2.79 g)

Sources & evidence

ORD record
ord-9de5a1fd27484fc692702ae359c0e05c
Source dataset
uspto-grants-1989_10
Patent number
US04876257

Reaction notes

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