Diisopropylethylamine → (E)-N-(2-(1-(3-(3,5-Dichlorophenyl)acryloyl)piperidin-4-yl)ethyl)-N-methyl-2-oxo-2,3-dihydrooxazole-5-carboxamide

HRID 1480425Notes

Reaction equation

HRID 1480425 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][NH:21][CH3:22])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[O:23]=[C:24]1[NH:28][CH:27]=[C:26]([C:29]([OH:31])=O)[O:25]1.CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C.CCOC(C)=O.O>[Cl:8][C:6]1[CH:5]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:14][CH2:15][CH:16]([CH2:19][CH2:20][N:21]([CH3:22])[C:29]([C:26]3[O:25][C:24](=[O:23])[NH:28][CH:27]=3)=[O:31])[CH2:17][CH2:18]2)=[O:12])[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 539814232-Hydroxy-1,3-oxazole-5-carboxylic acidHCID 86722656(E)-3-(3,5-dichlorophenyl)-1-(4-(2-(methylamino)ethyl)piperidin-1-yl)prop-2-en-1-one

Product 1

HCID 86722655(E)-N-(2-(1-(3-(3,5-Dichlorophenyl)acryloyl)piperidin-4-yl)ethyl)-N-methyl-2-oxo-2,3-dihydrooxazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the mixture containing (E)-3-(3,5-dichlorophenyl)-1-(4-(2-(methylamino)ethyl)piperidin-1-yl)prop-2-en-1-one (step 5) (118 mg, 0.346 mmol) and 2-oxo-2,3-dihydrooxazole-5-carboxylic acid (step 7) (2.59 ml, 0.2M solution in DMF, 0.519 mmol) and DIPEA (0.483 ml, 2.77 mmol) in DMF (3.458 ml) was added T3P® (50% solution in EtOAc) (2.421 ml, 4.149 mmol). The reaction mixture was stirred at RT for 1 h. Water was added to quench the excess T3P® and the solvent was removed under reduced pressure. The residue was passed through an Isolute SCX-2 cartridge (10 g) and washed with excess MeOH. The solvent was removed under reduced pressure to afford a yellow oil which was dried using a high vacuum oven. The crude material was purified using preparative HPLC with water (+0.1% TFA) and acetonitrile (+0.1% TFA) and the product fractions were concentrated under high vacuum to afford the title compound as a clear film;

Workup

  1. customto quench the excess T3P®
  2. customthe solvent was removed under reduced pressure
  3. washwashed with excess MeOH
  4. customThe solvent was removed under reduced pressure
  5. customto afford a yellow oil which
  6. customwas dried
  7. customThe crude material was purified
  8. concentrationthe product fractions were concentrated under high vacuum

Sources & evidence

ORD record
ord-1963cb55bda84bdbad0eaae01d776689
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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