Fumaric Acid → AZD-8055 fumarate

HRID 218358Notes

Reaction equation

HRID 218358 reaction equation
[CH3:1][C@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[N:9]=[C:10]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]2[CH3:34])[C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21]([O:26][CH3:27])=[C:22]([CH2:24][OH:25])[CH:23]=3)=[N:14][C:12]=2[N:13]=1.[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39]>O>[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].[CH3:1][C@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[N:9]=[C:10]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][C@@H:29]2[CH3:34])[C:11]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21]([O:26][CH3:27])=[C:22]([CH2:24][OH:25])[CH:23]=3)=[N:14][C:12]=2[N:13]=1

Participants

4

Reactant 2

HCID 444972Fumaric AcidHCID 25262965AZD 8055

Product 1

HCID 44537932AZD-8055 fumarate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
92 °C

Procedure

(5-{2,4-Bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)methanol prepared by the alternate method (10.00 g, 20.6 mmoles), fumaric Acid (2.63 g, 22.7 mmoles), water (84 ml) and methylated spirit industrial 74 O.P. (16.0 ml) were charged to a 250 ml reactor and heated to reflux (92° C.). The hot solution was filtered to remove extraneous matter. The filter was washed with a mixture of water (17 ml) and methylated spirit industrial 74 O.P. (3 ml) and heated to 60° C. Seed crystals of Formula 5a Fumarate are added to the filtrates to initiate crystallisation. The resulting suspension is held at 60° C. for 2 hours to establish crystallisation and the growth of suitably sized crystals. The desired product precipitated out on further cooling of the suspension. The product was isolated, washed with methylated spirit industrial 74 O.P. and dried to yield 10.12 g of (5-{2,4-Bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)methanol Fumarate as a yellow solid.

Workup

  1. addition(16.0 ml) were charged to a 250 ml reactor
  2. temperatureheated
  3. filtrationThe hot solution was filtered
  4. customto remove extraneous matter
  5. washThe filter was washed with a mixture of water (17 ml) and methylated spirit industrial 74 O.P
  6. temperature(3 ml) and heated to 60° C
  7. additionare added to the filtrates
  8. customcrystallisation
  9. customcrystallisation
  10. customThe desired product precipitated out
  11. temperatureon further cooling of the suspension
  12. customThe product was isolated
  13. washwashed with methylated spirit industrial 74 O.P
  14. customand dried

Sources & evidence

ORD record
ord-434077bfae1e4713bde89fe359db272f
Source dataset
uspto-grants-2012_06
Patent number
US08198441B2

Reaction notes

Loading…