Diisopropylethylamine → {3-[4-(1,1-Difluoroethyl)phenyl]-5-(3-ethoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl}(thiomorpholin-4-yl)methanone

HRID 661307Notes

Reaction equation

HRID 661307 reaction equation
[F:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][N:15]([C:17]([N:19]3[CH2:24][CH2:23][S:22][CH2:21][CH2:20]3)=[O:18])[CH2:14][CH:13]([C:25](O)=[O:26])[CH2:12]2)=[CH:7][CH:6]=1)([F:4])[CH3:3].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.O[N:62]=[C:63]([O:65][CH2:66][CH3:67])[NH2:64]>CN(C)C=O>[F:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:12][CH:13]([C:25]3[O:26][N:64]=[C:63]([O:65][CH2:66][CH3:67])[N:62]=3)[CH2:14][N:15]([C:17]([N:19]3[CH2:24][CH2:23][S:22][CH2:21][CH2:20]3)=[O:18])[CH2:16]2)=[CH:7][CH:6]=1)([F:4])[CH3:3]

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 581165495-[4-(1,1-Difluoroethyl)phenyl]-1-(thiomorpholin-4-ylcarbonyl)piperidine-3-carboxylic acidHCID 76223295ethyl N-hydroxyimidocarbamate

Product 1

HCID 58116565{3-[4-(1,1-Difluoroethyl)phenyl]-5-(3-ethoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl}(thiomorpholin-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 150 mg (0.376 mmol, 2:1 cis/trans isomer mixture) of the carboxylic acid from Example 73A in 5.2 ml of N,N-dimethylformamide were added, at RT, 172 mg (0.452 mmol) of HATU and 0.14 ml (0.83 mmol) of N,N-diisopropylethylamine, and the mixture was stirred for 30 min. Subsequently, the mixture was admixed with 43.1 mg (0.414 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] and then stirred at room temperature for 2 h. The reaction solution was purified directly by means of preparative HPLC. The resulting intermediate (118 mg) was taken up in toluene (24 ml), admixed with 4 Å molecular sieve and stirred under reflux overnight. The reaction solution was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by means of preparative HPLC. Yield: 55.4 mg (32% of theory)

Workup

  1. customThe reaction solution was purified directly by means of preparative HPLC
  2. stirringstirred
  3. temperatureunder reflux overnight
  4. filtrationThe reaction solution was filtered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-5b58148fcf1e4a5fb409ca5895fc0c76
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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