Hydrochloric Acid → HCID 178509920, compound

HRID 505508Notes

Reaction equation

HRID 505508 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][N:15]3[CH2:21][C:22]2[C:30]3[C:25](=[N:26][CH:27]=[CH:28][CH:29]=3)[N:24](C(OC(C)(C)C)=O)[N:23]=2)[CH:9]=1)[C:5]#[N:6].CN(C=O)C.Cl>CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][C:11]2[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][N:15]3[CH2:21][C:22]2[C:30]3[C:25](=[N:26][CH:27]=[CH:28][CH:29]=3)[NH:24][N:23]=2)[CH:9]=1)[C:5]#[N:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 68428075HCID 68428075, compound

Product 1

HCID 178509920HCID 178509920, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

A jacketed reaction vessel (30 L) equipped with a thermocouple was charged with 3-chloro-5-{[5-chloro-1-(1-t-butyloxycarbonyl-1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-indazol-4-yl]oxy}benzonitrile (1.338 kg; 2.499 moles; 1.0 eq.) and then with DMF (10.7 L) and IPA (2.68 L). Concentrated HCl (2.68 L) was then charged to the vessel during which time the internal temperature rose from 16° C. to 44° C. The mixture was then heated to 60° C. After 1 hour at 60° C., the suspension became a clear solution. Conversion was complete after 1.75 hours as determined by HPLC, at which point the reaction mixture was transferred into a 4-necked round bottom flask (75 L) at 55° C.-60° C. via an in-line filter. The reaction vessel was rinsed with IPA (2 L×2), and the rinse transferred to the flask via the in-line filter. Filtered water (16 L) was then added to the mixture via an additional funnel while maintaining the temperature at 55° C.-60° C., during which crystallization of the title product began. Upon completion of the water addition, the mixture was stirred at 55° C. for 40 minutes, then cooled to room temperature and filtered with a filter pot. The wet cake was rinsed with filtered IPA:water (3:7, 10 L), and then with filtered water (7 L×6), and then dried in a vacuum oven at 40° C. for two days to afford the title product.

Workup

  1. customA jacketed reaction vessel (30 L) equipped with a thermocouple
  2. customrose from 16° C. to 44° C
  3. waitConversion was complete after 1.75 hours
  4. customwas transferred into a 4-necked round bottom flask
  5. filtration(75 L) at 55° C.-60° C. via an in-line filter
  6. washThe reaction vessel was rinsed with IPA (2 L×2)
  7. filtrationin-line filter
  8. additionFiltered water (16 L) was then added to the mixture via an additional funnel
  9. temperaturewhile maintaining the temperature at 55° C.-60° C.
  10. customduring which crystallization of the title product
  11. additionUpon completion of the water addition
  12. temperaturecooled to room temperature
  13. filtrationfiltered with a filter pot
  14. washThe wet cake was rinsed with filtered IPA:water (3:7, 10 L)
  15. dry with materialwith filtered water (7 L×6), and then dried in a vacuum oven at 40° C. for two days

Sources & evidence

ORD record
ord-54508971993f480eada69c7c033f3d64
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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