Diisopropylethylamine → HCID 89402084, compound

HRID 1486980Notes

Reaction equation

HRID 1486980 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[NH:14][C:15](/[CH:18]=[CH:19]\[C:20]([OH:22])=O)=NN=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[F:26][C:27]1([F:31])[CH2:30][NH:29][CH2:28]1.[CH3:32][CH2:33][CH2:34]P(=O)=O.CCN(C(C)C)C(C)C>ClCCl.CO>[F:10][C:9]([F:11])([F:12])[C:7]1[CH:6]=[C:5]([C:13]2[N:14]=[C:15](/[CH:18]=[CH:19]/[C:20]([N:29]3[CH2:30][C:27]([F:31])([F:26])[CH2:28]3)=[O:22])[CH:34]=[CH:33][CH:32]=2)[CH:4]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:8]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 16167369Propylphosphoric anhydrideHCID 178525371HCID 178525371, compound

Product 1

HCID 89402084HCID 89402084, compoundYield 104.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

In a 50-mL round-bottomed flask Intermediate 2 (0.4 g, 1.1 mmol) and 3,3-difluoroazetidine hydrochloride (0.17 g, 1.3 mmol) was dissolved in dichloromethane (20 mL). Propylphosphonic anhydride (0.42 g, 1.3 mmol), DIPEA (0.28 g, 2.2 mmol) was added at room temperature and stirred reaction mixture for 30 min. The progress of the reaction was followed by TLC analysis on silica gel with 0.5% Methanol:dichloromethane as mobile phase and visualization with U.V light, reaction mixture was quenched into ice water slurry, filter it, compound was extracted in dichloromethane, dried over Na2SO4, filtered, and concentrated by rotary evaporation (28° C., 20 mmHg) to afford 0.5 g of a solid crude, The purification done by Flash chromatography and product elute at neat dichloromethane to afford pure compound 0.030 g yield (6.2%).

Workup

  1. customreaction mixture for 30 min
  2. customwas quenched into ice water slurry
  3. filtrationfilter it, compound
  4. extractionwas extracted in dichloromethane
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation (28° C., 20 mmHg)

Sources & evidence

ORD record
ord-dd9b8d637e9d4e45bbe90692ee97cbf1
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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