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

HRID 661300Notes

Reaction equation

HRID 661300 reaction equation
[N:1]1([C:7]([N:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:12][CH:11]([C:26](O)=[O:27])[CH2:10]2)=[O:8])[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.C[N:30]([C:32]([O:36]N1N=NC2C=CC=NC1=2)=[N+:33](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:53][CH2:54]N(C(C)C)C(C)C>CN(C)C=O>[CH2:53]([O:36][C:32]1[N:30]=[C:26]([CH:11]2[CH2:12][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:23])([F:25])[F:24])=[CH:17][CH:16]=3)[CH2:14][N:9]([C:7]([N:1]3[CH2:6][CH2:5][S:4][CH2:3][CH2:2]3)=[O:8])[CH2:10]2)[O:27][N:33]=1)[CH3:54]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581165211-(Thiomorpholin-4-ylcarbonyl)-5-[4-(2,2,2-trifluoroethyl)phenyl]piperidine-3-carboxylic acid

Product 1

HCID 58116557{3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-[4-(2,2,2-trifluoroethyl)phenyl]piperidin-1-yl}-(thiomorpholin-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 600 mg (1.08 mmol, purity 75%) of the carboxylic acid from Example 56A in 20.0 ml of N,N-dimethylformamide were added, at RT, 657 mg (1.73 mmol) of HATU and 0.57 ml (419 mg, 3.24 mmol) of N,N′-diisopropylethylamine, and the mixture was stirred for 30 min. Subsequently, the mixture was admixed with 225 mg (1.84 mmol, purity 85%) of ethyl W-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 was taken up in toluene (68 ml), admixed with 4 Å molecular sieve and stirred under reflux for 2 days. The reaction solution was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by means of preparative HPLC. Yield: 320 mg (61% of theory)

Workup

  1. customThe reaction solution was purified directly by means of preparative HPLC
  2. stirringstirred
  3. temperatureunder reflux for 2 days
  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-76ef861096de40c1b871aa28c52cc77c
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

Loading…