Phthalimide → (S)-2-(2-(3-bromopyrazolo[1,5-a]pyrimidin-5-ylamino)-3-methylbutyl)isoindoline-1,3-dione

HRID 539025Notes

Reaction equation

HRID 539025 reaction equation
[C:1]1(=[O:11])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](=[O:10])[NH:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:31][C:32]1[CH:33]=[N:34][N:35]2[CH:40]=[CH:39][C:38]([NH:41][C@@H:42]([CH:45]([CH3:47])[CH3:46])[CH2:43]O)=[N:37][C:36]=12.N(/C(OC(C)C)=O)=N\C(OC(C)C)=O>C1COCC1>[Br:31][C:32]1[CH:33]=[N:34][N:35]2[CH:40]=[CH:39][C:38]([NH:41][C@@H:42]([CH:45]([CH3:47])[CH3:46])[CH2:43][N:2]3[C:3](=[O:10])[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[C:1]3=[O:11])=[N:37][C:36]=12

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 67034301HCID 67034301, compound

Product 1

HCID 67033014(S)-2-(2-(3-bromopyrazolo[1,5-a]pyrimidin-5-ylamino)-3-methylbutyl)isoindoline-1,3-dioneYield 40.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of isoindoline-1,3-dione (4.9 g, 34 mmol) in THF cooled to 0° C. was added triphenylphosphine (8.8 g, 34 mmol) and (S)-2-(3-bromopyrazolo[1,5-a]pyrimidin-5-ylamino)-3-methylbutan-1-ol (Example 15, Step 1; 6.7 g, 22 mmol) and the reaction stirred at ambient temperature until all reactants were dissolved. To the reaction was added (E)-diisopropyl diazene-1,2-dicarboxylate (8.2 g, 40 mmol) and the reaction was stirred for 2 hours at ambient temperature. The reaction was concentrated in vacuo and the material chromatographed using 20% EtOAc/dichloromethane as eluent to yield (S)-2-(2-(3-bromopyrazolo[1,5-a]pyrimidin-5-ylamino)-3-methylbutyl)isoindoline-1,3-dione (3.8 g, 40%).

Workup

  1. dissolutionwere dissolved
  2. stirringthe reaction was stirred for 2 hours at ambient temperature
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe material chromatographed

Sources & evidence

ORD record
ord-17684601240a463a83d721305c980215
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

Loading…