Maleic Acid → GSK-2245035 maleate

HRID 2367969Notes

Reaction equation

HRID 2367969 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([O:11][C@@H:12]([CH3:16])[CH2:13][CH2:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:28])[N:6]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]\[C:32]([OH:34])=[O:33]>C(O)(C)C>[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]\[C:32]([OH:34])=[O:33].[NH2:1][C:2]1[N:10]=[C:9]([O:11][C@@H:12]([CH3:16])[CH2:13][CH2:14][CH3:15])[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:28])[N:6]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][N:22]1[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 44623937Gsk-2245035

Product 1

HCID 53342522GSK-2245035 maleateYield 69%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (for example, as prepared for Reference Example 1) (1.46 g, 3.74 mmol) in isopropyl alcohol (14.6 mL, 10 vols) was clarified (filtered at room temperature through a BondElut cartridge) and then heated to approximately 50° C. A solution of maleic acid (0.434 g, 3.74 mmol) in isopropyl alcohol (2.9 mL, 2 vols) was added. The resulting solution was then seeded and cooled to 45° C. Further seed was added. The resulting slurry was cooled to room temperature and held overnight (approximately 16 hours), then cooled in an ice/water bath for 30 minutes. The slurry was filtered, washing with isopropyl alcohol (4.5 mL, 3 vols and then 3 mL, 2 vols). The product was dried under reduced pressure at 40° C. to constant weight to give 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one, maleate salt (1.305 g, 69% th).

Workup

  1. filtrationfiltered at room temperature through a BondElut cartridge) and
  2. temperaturecooled to 45° C
  3. additionFurther seed was added
  4. temperatureThe resulting slurry was cooled to room temperature and held overnight (approximately 16 hours)
  5. temperaturecooled in an ice/water bath for 30 minutes
  6. filtrationThe slurry was filtered
  7. washwashing with isopropyl alcohol (4.5 mL, 3 vols
  8. customThe product was dried under reduced pressure at 40° C. to constant weight

Sources & evidence

ORD record
ord-aeda151f1f5f4df4997db1b757950475
Source dataset
uspto-grants-2014_04
Patent number
US08703754B2

Reaction notes

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