Diisopropylethylamine → [3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-(4-ethyl-3-fluorophenyl)piperidin-1-yl](thiomorpholin-4-yl)methanone

HRID 661311Notes

Reaction equation

HRID 661311 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][N:13]([C:15]([N:17]3[CH2:22][CH2:21][S:20][CH2:19][CH2:18]3)=[O:16])[CH2:12][CH:11]([C:23](O)=[O:24])[CH2:10]2)=[CH:5][C:4]=1[F:26])[CH3:2].O[N:28]=[C:29]([O:31][CH2:32][CH3:33])[NH2:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH2:32]([O:31][C:29]1[N:30]=[C:23]([CH:11]2[CH2:10][CH:9]([C:6]3[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[C:4]([F:26])[CH:5]=3)[CH2:14][N:13]([C:15]([N:17]3[CH2:22][CH2:21][S:20][CH2:19][CH2:18]3)=[O:16])[CH2:12]2)[O:24][N:28]=1)[CH3:33]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581165235-(4-Ethyl-3-fluorophenyl)-1-(thiomorpholin-4-ylcarbonyl)piperidine-3-carboxylic acidHCID 76223295ethyl N-hydroxyimidocarbamate

Product 1

HCID 58116583[3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-(4-ethyl-3-fluorophenyl)piperidin-1-yl](thiomorpholin-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

309 mg (0.81 mmol) of the compound from Example 36A and 169 mg (1.62 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] were initially charged in 3.1 ml of DMF and reacted with 463 mg (1.22 mmol) of HATU and 0.42 ml (315 mg, 2.44 mmol) of N,N-diisopropylethylamine. The mixture was stirred at RT for 15 minutes; the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed repeatedly with water, dried over sodium sulphate and concentrated under reduced pressure. The residue was taken up in 3.0 ml of DMF and converted at 180° C. for two minutes in the microwave (Emrys Optimizer). The reaction mixture was purified by means of preparative HPLC. Yield: 108 mg (30% of theory)

Workup

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. washThe organic phase was washed repeatedly with water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. waitconverted at 180° C. for two minutes in the microwave (Emrys Optimizer)
  6. customThe reaction mixture was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-d4144d93355c41dfa393deee53d215ac
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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