Hydrochloric Acid → HCID 71283223, compound

HRID 1752408Notes

Reaction equation

HRID 1752408 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:7]=[C:6]([N:24]2[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH:25]2[CH2:37][OH:38])[CH:5]=1)(=[O:3])[NH2:2].Cl>O1CCOCC1>[F:23][C:20]1[CH:21]=[CH:22][C:17]([O:16][C:13]2[CH:14]=[CH:15][C:10]([C:8]3[N:9]=[C:4]([C:1]([NH2:2])=[O:3])[CH:5]=[C:6]([N:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH:25]4[CH2:37][OH:38])[N:7]=3)=[CH:11][CH:12]=2)=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 90399278HCID 90399278, compound

Product 1

HCID 71283223HCID 71283223, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of the tert-butyl 4-(6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (0.848 g, 1.62 mmol) in dioxane (25 mL) was added 4M HCl in dioxane (5 mL, 20 mmol). After stirring overnight the reaction was concentrated in vacuo. The residue was triturated with 10 mL acetonitrile, filtered, and rinsed with 10 mL acetonitrile. The solid was then successively suspended and filtered three times from warm acetonitrile. The solid residue was then partitioned between 10 mL EtOAc and 2 mL 2M aqueous Na2CO3 solution. The mixture was diluted with 50 mL EtOAc and 25 mL water, the organic layer was removed and the aqueous emulsion was washed once more with 50 mL EtOAc. The aqueous emulsion was filtered off and rinsed with water. The resulting pasty solid was triturated with 2 mL acetonitrile, filtered, rinsed once with 1 mL acetonitrile, and dried under vacuum to give 2-(4-(4-fluorophenoxy)phenyl)-6-(2-(hydroxymethyl)piperazin-1-yl)pyrimidine-4-carboxamide as a pale tan powder (0.198 g, 0.468 mmol, 29% yield). 1H NMR (400 MHz, DMSO-d6): 8.52 (2H, d, J=8.8 Hz), 8.32 (1H, s), 7.78 (1H, s), 7.31-7.24 (2H, m), 7.22-7.12 (3H, m), 7.04 (2H, d, J=8.8 Hz), 4.85 (1H, s), 4.79-4.60 (1H, very broad s), 3.83-3.74 (1H, m), 3.56 (1H, br s), 3.17-3.09 (1H, m), 3.05-2.94 (2H, m), 2.73-2.65 (1H, m), 2.63-2.54 (1H, m), 2.49-2.32 (2H, m). LC/MS: m/z=424.2 [M+H]+.

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe residue was triturated with 10 mL acetonitrile
  3. filtrationfiltered
  4. washrinsed with 10 mL acetonitrile
  5. filtrationfiltered three times
  6. temperaturefrom warm acetonitrile
  7. customThe solid residue was then partitioned between 10 mL EtOAc and 2 mL 2M aqueous Na2CO3 solution
  8. additionThe mixture was diluted with 50 mL EtOAc and 25 mL water
  9. customthe organic layer was removed
  10. washthe aqueous emulsion was washed once more with 50 mL EtOAc
  11. filtrationThe aqueous emulsion was filtered off
  12. washrinsed with water
  13. customThe resulting pasty solid was triturated with 2 mL acetonitrile
  14. filtrationfiltered
  15. washrinsed once with 1 mL acetonitrile
  16. customdried under vacuum

Sources & evidence

ORD record
ord-39633d81b3ac4cfaa42cf4b492a13dff
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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