Acetic Acid → Apilimod

HRID 2076254Notes

Reaction equation

HRID 2076254 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][O:9][C:10]1[N:15]=[C:14]([NH:16][NH2:17])[CH:13]=[C:12]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:11]=1.[C:24]1([CH3:32])[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]=O)[CH:25]=1.C(O)(=O)C>CCOC(C)=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][O:9][C:10]1[N:15]=[C:14]([NH:16][N:17]=[CH:32][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[CH:25]=2)[CH:13]=[C:12]([N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[N:11]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 121053-MethylbenzaldehydeHCID 6723014-[6-Hydrazinyl-2-[2-(2-pyridinyl)ethoxy]-4-pyrimidinyl]morpholine2×

Product 1

HCID 49830988Apilimod

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A stirred suspension of 2-[2-(pyridin-2-yl)-ethoxy]-4-hydrazino-6-(morpholin-4-yl)-pyrimidine (Product 3) (5 g, 15.8 mmol, 95% purity), m-tolualdehyde (1.99 g, 16.6 mmol), ethyl acetate (25 mL) and acetic acid (45 μL) was heated to reflux for 15 minutes to give a clear solution. When TLC indicated that the reaction was completion, the reaction was allowed to cool to room temperature causing a solid precipitate to formed. The creamy solid was filtered out, washed with ethyl acetate (EtOAc) (3×5 mL) and dried to obtain crude Compound 6. The crude product (5 g, 75.6%) was dissolved in EtOAc (34 mL) under reflux. The resulting clear solution was concentrated to about 20 mL and cooled to room temperature causing Compound 6 to precipitate out forming a suspension. The suspension was stirred for 2 hours, then the precipitate was filtered out, washed with EtOAc (2×10 mL) and vacuum-dried to give Compound 6 as an off-white solid, 4.1 g (82%).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 15 minutes
  3. customto give a clear solution
  4. customto formed
  5. filtrationThe creamy solid was filtered out
  6. washwashed with ethyl acetate (EtOAc) (3×5 mL)
  7. customdried
  8. customto obtain crude Compound 6
  9. temperatureunder reflux
  10. concentrationThe resulting clear solution was concentrated to about 20 mL
  11. temperaturecooled to room temperature
  12. customto precipitate out
  13. customforming a suspension
  14. filtrationthe precipitate was filtered out
  15. washwashed with EtOAc (2×10 mL)
  16. customvacuum-dried

Sources & evidence

ORD record
ord-257380062183438e9d1091c659c770d5
Source dataset
uspto-grants-2011_04
Patent number
US07923557B2

Reaction notes

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