Theobromine → 1-[1-[1-(Bis(4-fluorophenyl)methyl]-piperazin-4-yl]-2-hydroxy-3-propanyl]-2,3, 6,7-tetrahydro-3,7-dimethyl-2,6-dioxo-1H-purine

HRID 1586701Notes

Reaction equation

HRID 1586701 reaction equation
[H-].[Na+].[NH:3]1[C:14](=[O:15])[C:13]2[N:11]([CH3:12])[CH:10]=[N:9][C:8]=2[N:6]([CH3:7])[C:4]1=[O:5].Cl[CH2:17][CH:18]([OH:41])[CH2:19][N:20]1[CH2:25][CH2:24][N:23]([CH:26]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:22][CH2:21]1>CS(C)=O>[F:33][C:30]1[CH:31]=[CH:32][C:27]([CH:26]([C:34]2[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=2)[N:23]2[CH2:22][CH2:21][N:20]([CH2:19][CH:18]([OH:41])[CH2:17][N:3]3[C:14](=[O:15])[C:13]4[N:11]([CH3:12])[CH:10]=[N:9][C:8]=4[N:6]([CH3:7])[C:4]3=[O:5])[CH2:25][CH2:24]2)=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 5429TheobromineHCID 24758Sodium hydrideHCID 103851541-(1-Chloro-2-hydroxy-3-propanyl)-4-(4,4'-difluorobenzhydryl)piperazine

Product 1

HCID 700581001-[1-[1-(Bis(4-fluorophenyl)methyl]-piperazin-4-yl]-2-hydroxy-3-propanyl]-2,3, 6,7-tetrahydro-3,7-dimethyl-2,6-dioxo-1H-purineYield 99.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To sodium hydride (0.3 g, 6.25 mmol of 50% with oil, prewashed with pentane) was added dry dimethyl sulfoxide (12 mL) and theobromine (0.9 g, 5 mmol). A fine suspension was formed to which was added 1-(1-chloro-2-hydroxy-3-propanyl)-4-(4, 4'-difluorobenzhydryl)piperazine (1.9 g, 5 mmol) dissolved in dry DMSO (10 mL) over 5 minutes. The mixture was stirred at room temperature under nitrogen for 24 hours and then heated to 70° C. for 20 hours. The DMSO was evaporated in vacuo (1 mmHg) at 75° C. and the residue was triturated in methylene chloride and filtered through Celite®. The filtrate was evaporated in vacuo to give a tacky solid (2.62 g) which was purified by flash chromatography over silica gel using 10% methanol/methylene chloride to give the desired product which was further purified with ether. The ether insoluble material was pure product (0.6 g, 25%), mp 138° -140° C.; DCI/MS: 525; 100 MHz 1H NMR (CDCl3)δ: 7.85 (s, 1H), 7.32 (m, 4H), 6.95 (m, 4H), 4.2 (s, IH), 4.1-4.22 (m, 3H), 3.97 (s, 3H), 3.57 (s, 3H), 2.3-2.5 (m, 10H).

Workup

  1. customA fine suspension was formed to which
  2. temperatureheated to 70° C. for 20 hours
  3. customThe DMSO was evaporated in vacuo (1 mmHg) at 75° C.
  4. customthe residue was triturated in methylene chloride
  5. filtrationfiltered through Celite®
  6. customThe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-a07db43464a84973a8a112fbff33bbf5
Source dataset
uspto-grants-1993_06
Patent number
US05215987

Reaction notes

Loading…