p-Toluenesulfonic acid monohydrate → HCID 178483312, compound

HRID 334172Notes

Reaction equation

HRID 334172 reaction equation
C(O[C:6](=O)[N:7]([CH:9]([C:11]1[N:12](C2CCCCO2)[C:13]2[C:18]([N:19]=1)=[C:17]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)[N:16]=[C:15]([Cl:26])[N:14]=2)[CH3:10])C)(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:26][C:15]1[N:14]=[C:13]2[C:18]([N:19]=[C:11]([CH:9]([NH:7][CH3:6])[CH3:10])[NH:12]2)=[C:17]([N:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)[N:16]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 86667383HCID 86667383, compound

Product 1

HCID 178483312HCID 178483312, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of {1-[2-chloro-6-morpholin-4-yl-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-ethyl}-methyl-carbamic acid tert-butyl ester (316 mg, 0.66 mmol) and p-toluenesulfonic acid monohydrate (30 mg) in methanol was stirred at room temperature for 3 h, then allowed to stand for 56h. The reaction mixture was concentrated in vacuo to a small volume, then DCM (3 mL) and trifluoroacetic acid (3 mL) were added and the reaction mixture was stirred for 4.75 h at RT. Another portion of trifluoroacetic acid (3 mL) was added and stirring was continued for 2 h. The mixture was concentrated in vacuo and the resulting residue was triturated three times with diethyl ether. The resulting solid was partitioned between a 10% solution of methanol in DCM and aqueous sodium bicarbonate. The phases were separated, and the aqueous phase was extracted four times with a 10% solution of methanol in DCM. The combined organic fractions were dried (Na2SO4), filtered and concentrated in vacuo to give [1-(2-Chloro-6-morpholin-4-yl-9H-purin-8-yl)-ethyl]-methyl-amine (0.19 g, 97%). LCMS RT=1.68 min, [M+H]+=297

Workup

  1. waitto stand for 56h
  2. concentrationThe reaction mixture was concentrated in vacuo to a small volume
  3. additionDCM (3 mL) and trifluoroacetic acid (3 mL) were added
  4. stirringthe reaction mixture was stirred for 4.75 h at RT
  5. additionAnother portion of trifluoroacetic acid (3 mL) was added
  6. stirringstirring
  7. waitwas continued for 2 h
  8. concentrationThe mixture was concentrated in vacuo
  9. customthe resulting residue was triturated three times with diethyl ether
  10. customThe resulting solid was partitioned between a 10% solution of methanol in DCM and aqueous sodium bicarbonate
  11. customThe phases were separated
  12. extractionthe aqueous phase was extracted four times with a 10% solution of methanol in DCM
  13. dry with materialThe combined organic fractions were dried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-efc9fda410f4443cb6b867b07216a647
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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