Triethylamine → 6-[1-[1-[Bis(4-fluorophenyl)methyl]piperazine-4-yl]-2-hydroxy-3-propanylthio]purine Hemihydrate

HRID 373624Notes

Reaction equation

HRID 373624 reaction equation
[SH:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.CCN(CC)CC.Cl[CH2:19][CH:20]([OH:43])[CH2:21][N:22]1[CH2:27][CH2:26][N:25]([CH:28]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[CH2:24][CH2:23]1>CN(C=O)C>[OH2:43].[F:35][C:32]1[CH:33]=[CH:34][C:29]([CH:28]([C:36]2[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=2)[N:25]2[CH2:24][CH2:23][N:22]([CH2:21][CH:20]([OH:43])[CH2:19][S:1][C:2]3[N:10]=[CH:9][N:8]=[C:7]4[C:3]=3[NH:4][CH:5]=[N:6]4)[CH2:27][CH2:26]2)=[CH:30][CH:31]=1.[F:42][C:39]1[CH:38]=[CH:37][C:36]([CH:28]([N:25]2[CH2:24][CH2:23][N:22]([CH2:21][CH:20]([OH:43])[CH2:19][S:1][C:2]3[N:10]=[CH:9][N:8]=[C:7]4[C:3]=3[NH:4][CH:5]=[N:6]4)[CH2:27][CH2:26]2)[C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)=[CH:41][CH:40]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 103851541-(1-Chloro-2-hydroxy-3-propanyl)-4-(4,4'-difluorobenzhydryl)piperazineHCID 178527888HCID 178527888, compound

Product 1

HCID 881248336-[1-[1-[Bis(4-fluorophenyl)methyl]piperazine-4-yl]-2-hydroxy-3-propanylthio]purine Hemihydrate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To DMF (7 mL), 6-mercaptopurine (5 mmol, 0.85 g) was added in portions and the solution was stirred at room temperature, under N2 for 5 min. Et3N (5 mmol, 0.69 mL) was added dropwise. After 5 min, 1-(1-chloro-2-hydroxy-3-propanyl)-4-[bis(4-fluorophenyl)-methyl]-piperazine (5 mmol, 1.9 g) in DMF (5 mL) was added dropwise over 5 min at room temperature under N2. After 22 h, the solution was filtered through a sintered glass funnel and the filtrate was evaporated (1.0 mm Hg, 50° C., stirring). Silica gel flash chromatography of the crude product (2.34 g) using 10% MeOH:CH2Cl2 gave pure product, 0.630 g (25.4%), mp 115°-116° C. (dec). DCI/MS (M+1) 497. 400 MHz 1H NMR (CDCl3)δ: 8.6 (s, 1H), 8.25 (s, 1H), 7.35 (m, 4H), 6.95 (m, 4H), 4.2 (s, 1H), 4.15 (m, 1H), 3.45 and 3.6 (m, 2H), 2.65 (m, 2H), 2.6 (m, 4H), 2.4 (m, 4H).

Workup

  1. waitAfter 5 min
  2. waitAfter 22 h
  3. filtrationthe solution was filtered through a sintered glass funnel
  4. customthe filtrate was evaporated
  5. stirring(1.0 mm Hg, 50° C., stirring)
  6. customCH2Cl2 gave pure product, 0.630 g (25.4%), mp 115°-116° C. (dec)

Sources & evidence

ORD record
ord-f01b3be98b3b4774aebec82de536500c
Source dataset
uspto-grants-1992_11
Patent number
US05164390

Reaction notes

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