Phosphoric Acid → 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one Dihydrogenphosphate

HRID 2042749Notes

Reaction equation

HRID 2042749 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10](=[O:35])[N:11]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]4[N:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)=[CH:22][N:21]=4)[CH:15]=3)[N:12]=2)[CH:4]=[N:3]1.[P:36](=[O:40])([OH:39])([OH:38])[OH:37]>O>[P:36]([OH:40])([OH:39])([OH:38])=[O:37].[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10](=[O:35])[N:11]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]4[N:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]5[CH2:30][CH2:31][O:32][CH2:33][CH2:34]5)=[CH:22][N:21]=4)[CH:15]=3)[N:12]=2)[CH:4]=[N:3]1

Participants

4

Reactant 2

HCID 1004Phosphoric AcidHCID 251346921100598-15-9

Product 1

HCID 462360536-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one Dihydrogenphosphate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
62 °C

Procedure

Approx. 15.2 kg of 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one (free base) were dispersed in approx. 31 kg DI water at T<30° C. After addition of approx. 5.5 kg aqueous phosphoric acid solution (85%), the solution was slurried for 30 minutes, and subsequently filtered. The resulting filtrate was diluted at 25° C. with approx. 55.8 kg acetone, resulting in a dispersion. The dispersion was heated to 62° C., resulting in a clear solution. The solution was cooled down to 50° C. (thermostat jacket temperature) with a defined cooling rate of 0.1 K/min, and slurried for approx. 6.5 hours, until a turbid dispersion was resulting. The dispersion was further cooled down to −10° C. (thermostat jacket temperature) with a defined cooling rate of 0.1 K/min, and post-slurried for approx. 1 hour at this temperature. The dispersion was filtered, and resulting crystals were washed with acetone and dried under vacuum at 70° C.

Workup

  1. filtrationsubsequently filtered
  2. additionThe resulting filtrate was diluted at 25° C. with approx. 55.8 kg acetone
  3. customresulting in a dispersion
  4. customresulting in a clear solution
  5. temperatureThe solution was cooled down to 50° C. (thermostat jacket temperature) with
  6. temperaturea defined cooling rate of 0.1 K/min
  7. waitslurried for approx. 6.5 hours, until a turbid dispersion
  8. customwas resulting
  9. temperatureThe dispersion was further cooled down to −10° C. (thermostat jacket temperature) with
  10. temperaturea defined cooling rate of 0.1 K/min
  11. waitpost-slurried for approx. 1 hour at this temperature
  12. filtrationThe dispersion was filtered
  13. customresulting crystals
  14. washwere washed with acetone
  15. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-92e2c868d8704f9db2f4dc335b10863a
Source dataset
uspto-grants-2013_11
Patent number
US08586599B2

Reaction notes

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