Toluene → 2-(benzo[b]thiophen-3-yl)-6-chloro-9-isopropyl-9H-purine

HRID 1422472Notes

Reaction equation

HRID 1422472 reaction equation
[Cl:1][C:2]1[N:10]=[C:9](I)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]([CH3:14])[CH3:13].[S:15]1[CH:19]=[C:18](B(O)O)[C:17]2[CH:23]=[CH:24][CH:25]=[CH:26][C:16]1=2.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[S:15]1[CH:19]=[C:18]([C:9]2[N:8]=[C:7]3[C:3]([N:4]=[CH:5][N:6]3[CH:12]([CH3:14])[CH3:13])=[C:2]([Cl:1])[N:10]=2)[C:17]2[CH:23]=[CH:24][CH:25]=[CH:26][C:16]1=2

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2776344(1-Benzothiophen-3-yl)boronic acidHCID 65389046-Chloro-2-iodo-9-isopropyl-9H-purine

Product 1

HCID 594089202-(benzo[b]thiophen-3-yl)-6-chloro-9-isopropyl-9H-purine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A round-bottom flask was charged with 6-chloro-2-iodo-9-isopropyl-9H-purine (prepared in Example 15c, 3.31 g, 0.0103 mol), benzo[b]thiophen-3-ylboronic acid (2.74 g, 0.0154 mol), and tetrakis(triphenylphosphine)palladium(0) (1.19 g, 0.0103 mol). To this mixture was added toluene (80 ml), ethanol (25 ml) and aqueous sodium carbonate solution (2M, 21 ml). The flask was sealed and the reaction mixture was stirred at 90° C. for 1 h. Water was added to the cooled mixture, which was extracted with ethyl acetate. The organic fractions were combined, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel, eluting with 20 to 50% EtOAc in hexane to afford the title compound as a solid, which was recrystallized from 1:1 methanol/water. 1H NMR (400 MHz, DMSO-d6): δ=9.15 (d, 1H), 8.85 (s, 2H), 8.17 (d, 1H), 7.62 (t, 1H), 7.53 (t, 1H), 5.06 (m, 1H), 1.71 (d, 6H); MS m/z 329.0 (M+1).

Workup

  1. customThe flask was sealed
  2. extractionwas extracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with 20 to 50% EtOAc in hexane

Sources & evidence

ORD record
ord-222493857d2f42d5b7338996f44b2e16
Source dataset
uspto-grants-2015_01
Patent number
US08927281B2

Reaction notes

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