1-Butanol → 8-[5-(1-Hydroxy-1-methylethyl)pyridin-3-yl]-1-[(2S)-2-methoxypropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one fumarate

HRID 244600Notes

Reaction equation

HRID 244600 reaction equation
[OH:1][C:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:20]=[CH:19][C:18]3[N:17]=[CH:16][C:15]4[N:21]([CH3:30])[C:22](=[O:29])[N:23]([CH2:24][C@@H:25]([O:27][CH3:28])[CH3:26])[C:14]=4[C:13]=3[CH:12]=2)[CH:8]=[N:9][CH:10]=1)([CH3:4])[CH3:3].C(O)CCC.[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40]>CCCCCCC>[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40].[OH:1][C:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:20]=[CH:19][C:18]3[N:17]=[CH:16][C:15]4[N:21]([CH3:30])[C:22](=[O:29])[N:23]([CH2:24][C@@H:25]([O:27][CH3:28])[CH3:26])[C:14]=4[C:13]=3[CH:12]=2)[CH:8]=[N:9][CH:10]=1)([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 2631-Butanol2×HCID 444972Fumaric Acid2×HCID 57519748Samotolisib

Product 1

HCID 681085528-[5-(1-Hydroxy-1-methylethyl)pyridin-3-yl]-1-[(2S)-2-methoxypropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one fumarate

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent2×

Conditions

Temperature
90 °C

Procedure

Example 5 can be prepared as by adding free base 8-[5-(1-hydroxy-1-methylethyl)pyridin-3-yl]-1-[(2S)-2-methoxypropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (60.2 mg) to 1-butanol (0.5 mL) and then add 21.9 mg fumaric acid. Add heptane (5×0.5 mL), which produces thick white slurry, and stir at 90° C./500 rpm. Vacuum filter and dry under nitrogen. Solids are lost during recovery from filtration, though sufficient for XRD. Additional crystalline fumarate salt is prepared by adding free base (101.0 mg) to 1-butanol (0.5 mL) and then add 34 mg fumaric acid. Add heptane (6×0.5 mL) and crystalline seeds of the fumarate salt from first preparation and stir the mixture at 90° C./500 rpm for 1 hour. Recover the solids by vacuum filtration and dry the solids under nitrogen. Further dry the solids in a vacuum oven (65° C.) overnight to provide the title compound.

Workup

  1. customExample 5 can be prepared as
  2. filtrationVacuum filter
  3. customdry under nitrogen
  4. filtrationSolids are lost during recovery from filtration
  5. stirringstir the mixture at 90° C./500 rpm for 1 hour
  6. customRecover the solids
  7. filtrationby vacuum filtration
  8. customdry the solids under nitrogen
  9. customFurther dry the solids in a vacuum oven (65° C.) overnight

Sources & evidence

ORD record
ord-a29cfa1c3e8840529cfc75fcc71f14da
Source dataset
uspto-grants-2014_02
Patent number
US08658668B2

Reaction notes

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