Diisopropylethylamine → HCID 86636933, compound

HRID 1366426Notes

Reaction equation

HRID 1366426 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][C@H:6]([CH3:10])[CH2:5]1.[CH3:11][C:12]([O:15][C:16]([N:18]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[N:19]([C:27]1[C:32]([F:33])=[C:31](Cl)[N:30]=[C:29]([Cl:35])[N:28]=1)[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[O:17])([CH3:14])[CH3:13].C(N(CC)C(C)C)(C)C>CN(C=O)C.CCOCC>[CH3:14][C:12]([O:15][C:16]([N:18]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[N:19]([C:27]1[C:32]([F:33])=[C:31]([N:7]2[CH2:8][CH2:9][N:4]([CH3:3])[CH2:5][C@H:6]2[CH3:10])[N:30]=[C:29]([Cl:35])[N:28]=1)[C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])=[O:17])([CH3:11])[CH3:13]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylateHCID 66935961HCID 66935961, compound

Product 1

HCID 86636933HCID 86636933, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To (3R)-1,3-dimethylpiperazine dihydrochloride (102.22 g, 546.3 mmol) was added a solution of tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (271.71 g, 546.3 mmol) in DMF (900 mL). The mixture was cooled to 0° C., and N,N-diisopropylethylamine (295 mL, 1694 mmol) was added. The solution was stirred and warmed to room temperature overnight. The solution was then diluted with Et2O (1000 mL) and washed with water (1000 mL). The aqueous phase was extracted with a fresh portion of Et2O (1000 mL), and the combined organic phase was washed with water (2×500 mL). The organic phase was then diluted with DCM (1000 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was filtered through a silica gel plug (30% EtOAc in hexanes; 1% Et3N). The solution was then concentrated in vacuo, and the residue was azeotroped with MeOH. The residue was diluted with MeOH (1000 mL), and crystallized by addition of water. The resulting solid was collected by vacuum filtration and washed with 10% MeOH in water. The resulting yellow solid was dried at 50° C. under high vacuum to give tris(1,1-dimethylethyl)2-{2-chloro-6-[(2R)-2,4-dimethyl-1-piperazinyl]-5-fluoro-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (257.34 g, 82% yield) as a light yellow solid. LCMS: (M+H)+: 575.2.

Workup

  1. temperaturewarmed to room temperature overnight
  2. washwashed with water (1000 mL)
  3. extractionThe aqueous phase was extracted with a fresh portion of Et2O (1000 mL)
  4. washthe combined organic phase was washed with water (2×500 mL)
  5. additionThe organic phase was then diluted with DCM (1000 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationThe residue was filtered through a silica gel plug (30% EtOAc in hexanes; 1% Et3N)
  10. concentrationThe solution was then concentrated in vacuo
  11. customthe residue was azeotroped with MeOH
  12. additionThe residue was diluted with MeOH (1000 mL)
  13. customcrystallized by addition of water
  14. filtrationThe resulting solid was collected by vacuum filtration
  15. washwashed with 10% MeOH in water
  16. customThe resulting yellow solid was dried at 50° C. under high vacuum

Sources & evidence

ORD record
ord-56377f77ed534125b41b6a50c546b31e
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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