Diisopropylethylamine → HCID 58378949, compound

HRID 1951156Notes

Reaction equation

HRID 1951156 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:4][N:3]=1.C[C@@H:20]1[NH:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1.[CH:33](N(C(C)C)CC)(C)C>CS(C)=O>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:2]([N:25]3[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])[C@@H:21]([CH3:33])[CH2:20]3)=[N:3][N:4]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 21152391-Chloro-4-(4-fluorophenyl)phthalazineHCID 7023035(S)-1-Boc-3-methylpiperazine

Product 1

HCID 58378949HCID 58378949, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

Add 1-chloro-4-(4-fluorophenyl)phthalazine (200 g, 773 mmol) to a solution of (S)-tert-butyl 3-methylpiperazine-1-carboxylate (232 g, 1.16 mol), diisopropylethylamine (674 mL, 28.1 mol), and DMSO (2.0 L). Heat the mixture to 120° C. for 60 h. Cool the mixture to 25° C., pour into ice water (3.0 L) and filter. Collect the solids, dissolve in CH2Cl2 (2.0 L), and extract with water (2.0 L). Concentrate the organic phase and add to a silica plug (3.0 kg silica) eluting with 3% THF in CH2Cl2 to yield the title compound as a yellow foam (126 g, 38%). ES/MS m/z 423.0 (M+1).

Workup

  1. temperatureCool the mixture to 25° C.
  2. filtrationfilter
  3. customCollect the solids
  4. dissolutiondissolve in CH2Cl2 (2.0 L)
  5. extractionextract with water (2.0 L)
  6. concentrationConcentrate the organic phase
  7. additionadd to a silica plug (3.0 kg silica)
  8. washeluting with 3% THF in CH2Cl2

Sources & evidence

ORD record
ord-782bc87ba2454c238b0e78ec9b912941
Source dataset
uspto-grants-2013_03
Patent number
US08404687B2

Reaction notes

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