4-Methylmorpholine → 1,1-Dimethylethyl [1-({2,4-difluoro-6-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]carbamate

HRID 605698Notes

Reaction equation

HRID 605698 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])[C:3]=1[C:4]([OH:6])=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH:61]1[CH2:64][CH:63]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:71])([CH3:70])[CH3:69])[CH2:62]1>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])[C:3]=1[C:4]([N:61]1[CH2:64][CH:63]([NH:65][C:66](=[O:72])[O:67][C:68]([CH3:70])([CH3:69])[CH3:71])[CH2:62]1)=[O:6]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 15194053-Aminoazetidine, 3-BOC protectedHCID 2724699PyBOPHCID 670515602,4-Difluoro-6-((2-fluoro-4-iodophenyl)amino)benzoic acid

Product 1

HCID 691030281,1-Dimethylethyl [1-({2,4-difluoro-6-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]carbamateYield 91.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,4-Difluoro-6-[(2-fluoro-4-iodophenyl)amino]benzoic acid (100 mg, 0.25 mmol) was taken into DMF (1 mL) followed by addition of PyBOP (137 mg, 0.26 mmol) and the mixture was stirred for 15 minutes then NMM (60 μL, 0.5 mmol) and commercially available 1,1-dimethylethyl azetidin-3-ylcarbamate (43 mg, 0.25 mmol) were subsequently added. The mixture was allowed to stir for 12 hours at room temperature then partitioned with ethyl acetate and water. The organic phase was washed three times with additional water then brine and dried over anhydrous sodium sulfate. Filtration and concentration followed by silica gel flash chromatography of the residue using hexanes:ethyl acetate 3:1 as eluent afforded 1,1-dimethylethyl [1-({2,4-difluoro-6-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]carbamate (125 mg) as a colorless oil.

Workup

  1. stirringto stir for 12 hours at room temperature
  2. customthen partitioned with ethyl acetate and water
  3. washThe organic phase was washed three times with additional water
  4. dry with materialbrine and dried over anhydrous sodium sulfate
  5. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-59290305f88949608ce3e0f46275c4dc
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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