4-Nitrobenzyl bromide → HCID 14802629, compound

HRID 2254547Notes

Reaction equation

HRID 2254547 reaction equation
[OH:1][CH2:2][CH2:3][S:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[C:20]3[N:19]=[CH:18][N:17]=[C:15]([NH2:16])[C:14]=3[N:13]=[CH:12]2)[C@H:8]([OH:21])[C@@H:7]1[OH:22].[N+:23]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1)([O-:25])=[O:24]>CN(C=O)C>[OH:1][CH2:2][CH2:3][S:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[C:20]3[N:19]=[CH:18][N:17]=[C:15]([NH:16][CH2:30][C:29]4[CH:32]=[CH:33][C:26]([N+:23]([O-:25])=[O:24])=[CH:27][CH:28]=4)[C:14]=3[N:13]=[CH:12]2)[C@H:8]([OH:21])[C@@H:7]1[OH:22]

Participants

4

Reactant 2

HCID 660114-Nitrobenzyl bromideHCID 9862185(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-(2-hydroxyethylsulfanylmethyl)oxolane-3,4-diol

Product 1

HCID 14802629HCID 14802629, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of triol 1b (650 mg, 2.0 mmol), 4-nitrobenzyl bromide (2.16 g, 10 mmol), and powdered 4A molecular sieves (2.0 g) in dry DMF (15 mL was stirred for 4 days in a stoppered flask at ambient temperature, and filtered. The filtrate was concentrated under reduced pressure and the resulting crystalline mass was triturated with acetone (3×) and toluene (3×). The solid residue was dissolved in MeOH (10 mL) and treated with NH3 /MeOH (10 mL; w/v, 1:1, prepared at -10° C.). This solution was stirred for 5 h at ambient temperature and concentrated to a red gum. The gum was dissolved in hot MeOH and cooled to give a brown solid that was recrystallized from MeOH to give title compound 2 as red needles (360 mg, 39%). The mother liquors were concentrated and the residue subjected to flash chromatography (MeOH/CHCl3, 2:23) to give a red solid that was recrystallized to give further red needles (165 mg, 19%) of 2 (total 57%) with mp 157°-158° C.; UV (MeOH) max 270 nm (ε 24 700), HCl/MeOH) max 274 nm (ε 29 900), (NaOH/MeOH) max 271 nm (ε 24 500); IH NMR (Me2SO-d6) δ 8.62 (br s, 1, NH), 8.46 (s, 1, H8), 8.26 (s, 1, H2), 8.20 (d, JAB =8.8 Hz, 2, Ar), (d, 2, Ar), 5.96 (d, J1'-2' =5.7 Hz, 1, H1'), 5.56 (d, JOH-2' =5.8 Hz, 1, OH2'), 5.39 (d, JOH-3' =5.0 Hz, 1, OH3'), 4.85 (br s, 2, CH2Ar), 4.81 (t, J2'-3' =5.4 Hz, 1, H2' ), 4.18 (br q, J3'-4' =4.0 Hz, 1, H3'), 4.05 (m, J4'-5'a =6.0 Hz, J4'-5'b =7.2 Hz, 1, H4'), 3.54 (dt, J=5.5 Hz, 2, CH2OH2.97 (m, J5'a-5'b =13.8 Hz, 1, H5'a), 2.87 (m, 1, H5'b), 2.62 (t, 2, SCH2); 13C NMR (Me2SO-d6) δ 154.32 (C6), 152.56 (C2), 149.31 (Ar), 148.26 (C4), 146.35 (Ar), 140.13 (C8), 128.01 (Ar), 123.44 (Ar), 120.01 (C5), 87.44 (C1'), 84.04 (C4'), 72.71, 72.54 (C2',3'), 60.85 (CH2OH), 43.31 (CH2Ar), 34.63 (C5' ), 34.30 (SCH2); MS m/z 417.0969 [C17H17N6O5S (M-C2H5O)=417.0981]. Anal. Calcd for C19H22N6O6S (462.5): C, 49.34; H, 4.79; N, 18.17. Found: c, 48.99; H, 4.70; N, 18.04

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customthe resulting crystalline mass was triturated with acetone (3×) and toluene (3×)
  4. dissolutionThe solid residue was dissolved in MeOH (10 mL)
  5. additiontreated with NH3 /MeOH (10 mL; w/v, 1:1, prepared at -10° C.)
  6. stirringThis solution was stirred for 5 h at ambient temperature
  7. concentrationconcentrated to a red gum
  8. dissolutionThe gum was dissolved in hot MeOH
  9. temperaturecooled
  10. customto give a brown solid that
  11. customwas recrystallized from MeOH

Sources & evidence

ORD record
ord-3eeefd6530d0449f9925e2c072489313
Source dataset
uspto-grants-1993_08
Patent number
US05236902

Reaction notes

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