Diisopropylethylamine → HCID 90462363, compound

HRID 588845Notes

Reaction equation

HRID 588845 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([O:15][CH3:16])=[C:10]([C:17]([N:19]2[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=[O:26])[CH2:21][CH2:20]2)=[O:18])[CH:9]=1.Cl.CO.[CH3:35][N:36]([CH3:43])[CH2:37][CH:38]=[CH:39]C(O)=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(OCC)(=O)C.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([O:15][CH3:16])=[C:10]([C:17]([N:19]2[CH2:20][CH2:21][N:22]([C:25](=[O:26])/[CH:39]=[CH:38]/[CH2:37][N:36]([CH3:43])[CH3:35])[CH2:23][CH2:24]2)=[O:18])[CH:9]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 21893726Hydrochloride methanolHCID 533952454-(Dimethylamino)but-2-enoic acidHCID 117607168HCID 117607168, compound

Product 1

HCID 90462363HCID 90462363, compoundYield 201%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-Butyl 4-(2′,6-dichloro-4-methoxy-[1,1′-biphenyl]-3-carbonyl)piperazine-1-carboxylate (550 mg, 1.18 mmol) in HCl/MeOH (20 mL, 57.2 mmol) was stirred at room temperature for 1 h. The solvent was removed under reduced pressure to yield the crude product. The crude residue was dissolved with DMF (10 mL), 4-(dimethylamino)but-2-enoic acid (215 mg, 0.47 mmol), BOP (627 mg, 1.42 mmol) and DIEA (610 mg, 4.73 mmol) was added. The resulting mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1) to afford the desired product (450 mg, 80% yield, 2 steps). ESI-MS m/z: 476.4[M+H]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto yield the crude product
  3. additionwas added
  4. stirringThe resulting mixture was stirred at room temperature for 2 h
  5. washwashed with brine
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1)

Sources & evidence

ORD record
ord-6afc1ca7c11f401fa7a74efcb25975fd
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

Loading…