Triethylamine → 2-Amino-6-[1-[1-[bis(4-fluorophenyl)methyl]piperazin-4-yl]-2-hydroxy-3-propanyl-thio]purine Hemihydrate

HRID 1493547Notes

Reaction equation

HRID 1493547 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([SH:11])[N:3]=1.C(N(CC)CC)C.Cl[CH2:20][CH:21]([OH:44])[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>[OH2:44].[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([S:11][CH2:20][CH:21]([OH:44])[CH2:22][N:23]2[CH2:24][CH2:25][N:26]([CH:29]([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)[C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)[CH2:27][CH2:28]2)[N:3]=1.[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([S:11][CH2:20][CH:21]([OH:44])[CH2:22][N:23]2[CH2:24][CH2:25][N:26]([CH:29]([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)[C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)[CH2:27][CH2:28]2)[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 103851541-(1-Chloro-2-hydroxy-3-propanyl)-4-(4,4'-difluorobenzhydryl)piperazineHCID 178509034HCID 178509034, compound

Product 1

HCID 885274672-Amino-6-[1-[1-[bis(4-fluorophenyl)methyl]piperazin-4-yl]-2-hydroxy-3-propanyl-thio]purine HemihydrateYield 81.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 2-amino-6-mercaptopurine (10 mmol, 1.67 g) in DMF (25 mL) was added triethylamine (10 mmol, 1.4 mL). After stirring about 5 min, 1-(1-chloro-2-hydroxy-3-propanyl)-4-(4,4'-difluorobenzhydryl)piperazine (10 mmol, 3.81 g) in DMF (20 mL) was added dropwise over 5 min. under nitrogen. After one week, the DMF was removed in vacuo and the resultant crude solid was flash chromatographed over silica gel using 5% MeOH: CH2Cl2 to give the desired product (2.82 g, 55.1%) as a white solid, mp 118°-122° C. (dec.). MS DCI (M+1) 512; (400 MHz) 1H NMR (CDCl3) δ: 7.9 (s, 1H); 7.3 (m, 4H), 6.95 (m, 4H), 4.2 (s, 1H), 4.15 (m, 1H), 3.3 (m, 2H), 2.3-2.6 (m, 10H).

Workup

  1. waitAfter one week
  2. customthe DMF was removed in vacuo
  3. customchromatographed over silica gel using 5% MeOH

Sources & evidence

ORD record
ord-13b5685ca7cd49caa23fc30173028831
Source dataset
uspto-grants-1991_06
Patent number
US05021574

Reaction notes

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