Diisopropylethylamine → Ethyl 3-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoate

HRID 2374058Notes

Reaction equation

HRID 2374058 reaction equation
[NH2:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=2)=[C:4]([F:18])[CH:3]=1.C(OC1C=CC(NC2N=CN=C(OC3C=CC(NC(=O)CC(NC4C=CC(F)=CC=4)=O)=CC=3F)C=2)=CC=1)C1C=CC=CC=1.CCN(C(C)C)C(C)C.Cl[C:72](=[O:79])[CH2:73][C:74]([O:76][CH2:77][CH3:78])=[O:75]>CN(C=O)C.CCOC(C)=O>[C:13]([C:9]1[CH:8]=[C:7]([O:6][C:5]2[CH:16]=[CH:17][C:2]([NH:1][C:72](=[O:79])[CH2:73][C:74]([O:76][CH2:77][CH3:78])=[O:75])=[CH:3][C:4]=2[F:18])[CH:12]=[CH:11][N:10]=1)(=[O:14])[NH2:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 118931Ethyl 3-chloro-3-oxopropionate2×HCID 231532054-(4-Amino-2-fluorophenoxy)picolinamideHCID 59853038N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

Product 1

HCID 59853090Ethyl 3-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoateYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 1.0 g, 4.0 mmol) in DMF (10.0 mL) were added DIEA (2.0 mL) and ethyl 3-chloro-3-oxopropanoate (Aldrich, 0.75 mL, 6.0 mmol). The mixture was stirred at room temperature for 12 h and more ethyl 3-chloro-3-oxopropanoate (0.20 mL, 1.6 mmol) was added. The mixture was stirred for 2 h and was then diluted with EtOAc (200 mL). It was washed with H2O and brine and then dried over MgSO4. After filtration and concentration, the residue was triturated with DCM and filtered to give ethyl 3-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-3-oxopropanoate (900 mg, 62% yield). MS(ESI+) m/z 362.28 (M+H)+.

Workup

  1. stirringThe mixture was stirred for 2 h
  2. washIt was washed with H2O and brine
  3. dry with materialdried over MgSO4
  4. filtrationAfter filtration and concentration
  5. customthe residue was triturated with DCM
  6. filtrationfiltered

Sources & evidence

ORD record
ord-74e9497fe0a64a5392a558265a5f9335
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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