Sodium hydride → 9-((3-o-tolylbenzo[b]thiophen-2-yl)methyl)-9H-purin-6-amine

HRID 243346Notes

Reaction equation

HRID 243346 reaction equation
[H-].[Na+].[N:3]1[C:11]([NH2:12])=[C:10]2[C:6]([NH:7][CH:8]=[N:9]2)=[N:5][CH:4]=1.CS(O[CH2:18][C:19]1[S:23][C:22]2[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=2[C:20]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH3:34])(=O)=O>CN(C=O)C>[C:29]1([CH3:34])[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[C:20]1[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[S:23][C:19]=1[CH2:18][N:7]1[CH:8]=[N:9][C:10]2[C:6]1=[N:5][CH:4]=[N:3][C:11]=2[NH2:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86668875(3-o-Tolylbenzo[b]thiophen-2-yl)methyl methanesulfonateHCID 178508693HCID 178508693, compound

Product 1

HCID 601620369-((3-o-tolylbenzo[b]thiophen-2-yl)methyl)-9H-purin-6-amineYield 67.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

NaH (60% in mineral oil, 16 mg, 0.39 mmol) was added in one portion to a mixture of 9H-purin-6-ylamine (49 mg, 0.36 mmol) in DMF (5 mL) at RT. After 5 min stirring, a solution of methanesulfonic acid 3-o-tolylbenzo[b]thiophen-2-ylmethyl ester from Example 27 (100 mg, 0.30 mmol) in DMF (1 mL) was added dropwise and stirring at RT was continued for 19 h. The reaction mixture was then quenched by addition of water and a solid formed. The precipitated was collected by filtration and was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) affording 167 as a white solid (75 mg, 67%). LCMS: RT 4.13 min [M+H]+ 372.1. 1H NMR (DMSO, 400 MHz): δ 8.11 (1H, s), 7.96-7.88 (2H, m), 7.45-7.30 (6H, m), 7.23 (2H, s), 7.12-7.07 (1H, m), 5.46 (1H, d, J=16.2 Hz), 5.38 (1H, d, J=16.2 Hz), 1.99 (3H, s)

Workup

  1. stirringstirring at RT
  2. waitwas continued for 19 h
  3. customThe reaction mixture was then quenched by addition of water
  4. customa solid formed
  5. filtrationThe precipitated was collected by filtration
  6. customwas purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-c6d474812cd145e0807bac9f0f7204a6
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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