Ethyl Acetate → HCID 178485296, compound

HRID 392987Notes

Reaction equation

HRID 392987 reaction equation
[CH:1]1([N:7]2[C:11]3=[N:12][CH:13]=[C:14]([C:16]4[N:20](CCC#N)[N:19]=[N:18][N:17]=4)[CH:15]=[C:10]3[N:9]=[C:8]2[C:25]2[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:33][C:34]1[CH:39]=[C:38]([C:40]([NH:42][CH3:43])=[O:41])[CH:37]=[CH:36][C:35]=1[C:44]1[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[CH:46][CH:45]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CN(C)C=O>[CH3:43][NH:42][C:40]([C:38]1[CH:37]=[CH:36][C:35]([C:44]2[CH:49]=[CH:48][C:47]([C:50]#[N:51])=[CH:46][CH:45]=2)=[C:34]([CH2:33][O:31][C:28]2[CH:29]=[CH:30][C:25]([C:8]3[N:7]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)[C:11]4=[N:12][CH:13]=[C:14]([C:16]5[NH:17][N:18]=[N:19][N:20]=5)[CH:15]=[C:10]4[N:9]=3)=[CH:26][CH:27]=2)[CH:39]=1)=[O:41]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 22660779HCID 22660779, compoundHCID 135674092HCID 135674092, compound

Product 1

HCID 178485296HCID 178485296, compoundYield 8.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate 63 (50 mg, 0.12 mmol) in dimethylformamide was reacted with 2-(bromomethyl)-4′-cyano-N-methyl-1,1′-biphenyl-4-carboxamide (63a) (40 mg, 0.12 mmol), cesium carbonate (20 mg, 0.06 mmol) and the resulting suspension stirred under a nitrogen atmosphere at rt for 3h at which point ethyl acetate (30 mL) was added. The organic phase was washed with water (2×25 mL) and brine (1×), dried (Na2SO4), and concentrated on a rotary evaporator. The resulting residue was dissolved in 10% methanolic sodium hydroxide (5 mL) and water (2 mL) was added. The resulting solution was stirred at rt under a nitrogen atmosphere for 30 minutes at which point 10% hydrochloric acid was added until pH=2. This solution was extracted with ethyl acetate, dried (Na2SO4), and concentrated on a rotary evaporator and the residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford the product as a white solid (6 mg, 7%). 1H NMR (CD3OD) δ 9.16 (s, 1H), 8.7 (br s, 1H), 8.15 (d, 1H, J=1.46), 7.94 (dd, 1H, J=8.06, 1.83), 7.80 (d, 2H, J=8.42), 7.71 (br m, 2H), 7.65 (d, 2H, J=8.06), 7.49 (d, 1H, J=8.06), 7.17 (d, 2H, 6.59), 5.14 (s, 1H), 4.46 (br m, 1H), 2.96 (s, 3H), 2.83 (br m, 2H), 1.96 (br m, 4H), 1.75 (br m, 1H), 1.39 (br m, 3H); ESI-MS m/e 610.24 (M+H); HPLC purity (ELSD)>95%.

Workup

  1. additionwas added
  2. washThe organic phase was washed with water (2×25 mL) and brine (1×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated on a rotary evaporator
  5. dissolutionThe resulting residue was dissolved in 10% methanolic sodium hydroxide (5 mL)
  6. additionwater (2 mL) was added
  7. additionwas added until pH=2
  8. extractionThis solution was extracted with ethyl acetate
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated on a rotary evaporator
  11. customthe residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-53cb1069a0074889beeef1b782acfa63
Source dataset
uspto-grants-2004_10
Patent number
US06803374B2

Reaction notes

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