1-Phenethylamine → HCID 59852962, compound

HRID 1670326Notes

Reaction equation

HRID 1670326 reaction equation
[C:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[C:16]([F:17])=[CH:15][C:14]([NH:18][C:19](=[O:24])[CH2:20][C:21]([OH:23])=O)=[C:13]([F:25])[CH:12]=2)[CH:7]=[CH:6][N:5]=1)(=[O:3])[NH2:2].[C:26]1([CH:32]([NH2:34])[CH3:33])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:17][C:16]1[CH:15]=[C:14]([NH:18][C:19](=[O:24])[CH2:20][C:21](=[O:23])[NH:34][CH:32]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH3:33])[C:13]([F:25])=[CH:12][C:11]=1[O:10][C:8]1[CH:7]=[CH:6][N:5]=[C:4]([C:1]([NH2:2])=[O:3])[CH:9]=1

Participants

5

Reactant 3

HCID 74081-PhenethylamineHCID 81531DiisopropylethylamineHCID 59853078HCID 59853078, compound

Product 1

HCID 59852962HCID 59852962, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a homogeneous mixture of 3-(4-(2-carbamoylpyridin-4-yloxy)-2,5-difluorophenylamino)-3-oxopropanoic acid (89 mg, 0.25 mmol) and (±)-1-phenyl-ethanamine (Aldrich, 0.05 mL, 0.38 mmol) in DMF (3 mL) was added DIPEA (0.07 mL, 0.38 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uranium hexafluorophosphate (TBTU) (121 mg, 0.38 mmol). The resulting solution was stirred for 15 hours before being quenched with 10% LiCl (aq). The mixture was partitioned between EtOAc and 10% LiCl (aq), the layers separated, and the aqueous layer extracted with EtOAc. The combined organic layers were washed twice with 10% LiCl (aq), then concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 1:3 hexane/EtOAc) and the appropriate fractions were concentrated in vacuo to afford the title compound (42 mg, 37%). HRMS (ESI+), 455.1532 (M+H)+ calcd., 455.1528 (M+H)+ found.

Workup

  1. custombefore being quenched with 10% LiCl (aq)
  2. customThe mixture was partitioned between EtOAc and 10% LiCl (aq)
  3. customthe layers separated
  4. extractionthe aqueous layer extracted with EtOAc
  5. washThe combined organic layers were washed twice with 10% LiCl (aq)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (eluting with 1:3 hexane/EtOAc)
  8. concentrationthe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-b571b57cd8eb487ca023e72538f97a7a
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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