p-Toluenesulfonic acid monohydrate → 4-(2-chloro-9H-purin-6-yl)morpholine

HRID 1692864Notes

Reaction equation

HRID 1692864 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2C2CCCCO2)=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)[N:3]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 134629464-(2-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine

Product 1

HCID 32746034-(2-chloro-9H-purin-6-yl)morpholine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 4-(2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine (100 g) in methanol (500 mL) at 50° C. was added p-toluenesulfonic acid monohydrate (6 g). The reaction was stirred for 30 mins, whereupon white solid has crashed fully out of solution. The solid was filtered and collected through a Buchner funnel, rinsed with methanol and dried under vacuum to get 4-(2-chloro-9H-purin-6-yl)morpholine. Cesium carbonate (200 g) and iodomethane (30 mL) were subsequently added to a stirring solution of 4-(2-chloro-9H-purin-6-yl)morpholine in DMF at 50° C. The reaction was monitored by lc-ms until complete, about 30 minutes, whereupon the solvent was concentrated to dryness. Subsequent suspension of the crude reaction in water crashed out 4-(2-chloro-9-methyl-9H-purin-6-yl)morpholine (72 g) as a white solid, which was filtered and dried under vacuum overnight.

Workup

  1. filtrationThe solid was filtered
  2. customcollected through a Buchner funnel
  3. washrinsed with methanol
  4. customdried under vacuum

Sources & evidence

ORD record
ord-d5f706eff9b24be5b57bd33351ec2cbb
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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