Hydrochloric Acid → 4-[2-(4-amino-cyclohexylamino)-9-cyclopentyl-9H-purin-6-ylamino]-piperidine-1-sulfonic acid methylamide

HRID 33364Notes

Reaction equation

HRID 33364 reaction equation
[CH3:1][NH:2][S:3](Cl)(=[O:5])=[O:4].O1CCCC1.C(OC(=O)[NH:18][C@H:19]1[CH2:24][CH2:23][C@H:22]([NH:25][C:26]2[N:34]=[C:33]3[C:29]([N:30]=[CH:31][N:32]3[CH:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)=[C:28]([NH:40][CH:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)[N:27]=2)[CH2:21][CH2:20]1)(C)(C)C.Cl>O1CCOCC1>[CH3:1][NH:2][S:3]([N:44]1[CH2:45][CH2:46][CH:41]([NH:40][C:28]2[N:27]=[C:26]([NH:25][CH:22]3[CH2:23][CH2:24][CH:19]([NH2:18])[CH2:20][CH2:21]3)[N:34]=[C:33]3[C:29]=2[N:30]=[CH:31][N:32]3[CH:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)[CH2:42][CH2:43]1)(=[O:5])=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 11789235N-Methylsulfamoyl chlorideHCID 178454031HCID 178454031, compound2×

Product 1

HCID 690231244-[2-(4-amino-cyclohexylamino)-9-cyclopentyl-9H-purin-6-ylamino]-piperidine-1-sulfonic acid methylamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
55 °C

Procedure

Treat a stirred, cooled (0° C.) solution of N-methyl sulfamoyl chloride (0.2 mmol) and anhydrous tetrahydrofuran (275 mL) with a solution of trans-{4-[9-cyclopentyl-6-(piperidin-4-ylamino)-9H-purin-2-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (9a, 0.2 mmol) triethylamine (9a 0.2 mmol) and tetrahydrofuran (4 mL) overnight at room temperature. Warm to 55° C., cool to room temperature and add 1.0 ml of 4N HCl in dioxane. Allow to stand for 3 hours, concentrate and dissolve the residue in DCM using a small amount of methanol as co-solvent if necessary. Purify the product by chromatography on a 2 g silica gel SPE cartridge pre-equilibrated with heptane. Elute the column in three fractions; first fraction 5 ml DCM; fractions 2 and 3 with 10-15 ml of DCM/methanol (4:1). Concentrate the desired fractions, dissolve the residue in ethanol and adjust to pH 2.0 with 10% HCl. Concentrate to dryness to give 4-[2-(4-amino-cyclohexylamino)-9-cyclopentyl-9H-purin-6-ylamino]-piperidine-1-sulfonic acid methylamide. Using N,N-dimethyl sulfamoyl chloride under similar conditions provides the corresponding trans-4-[2-(4-amino-cyclohexylamino)-9-cyclopentyl-9H-purin-6-ylamino]-piperidine-1-sulfonic acid dimethylamide. The corresponding 9-isopropyl and 9-cyclopent-2-enyl compound I sulfonic acid amides are prepared in a similar manner from 9b and 9c.

Workup

  1. additionTreat a stirred
  2. temperaturecool to room temperature
  3. concentrationconcentrate
  4. dissolutiondissolve the residue in DCM using a small amount of methanol as co-solvent if necessary
  5. customPurify the product by chromatography on a 2 g silica gel SPE cartridge pre-equilibrated with heptane
  6. washElute the column in three fractions
  7. concentrationConcentrate the desired fractions
  8. dissolutiondissolve the residue in ethanol
  9. concentrationConcentrate to dryness

Sources & evidence

ORD record
ord-8ee47f349abc492e8cdd53ae2d8f8355
Source dataset
uspto-grants-2008_09
Patent number
US07429595B2

Reaction notes

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