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

HRID 661305Notes

Reaction equation

HRID 661305 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]2[CH2:18][N:17]([C:19]([N:21]3[CH2:26][CH2:25][S:24][CH2:23][CH2:22]3)=[O:20])[CH2:16][CH:15]([C:27](O)=[O:28])[CH2:14]2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]([F:12])([F:11])[F:10].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:64]=[C:65]([O:67][CH2:68][CH3:69])[NH2:66]>CN(C)C=O>[CH2:68]([O:67][C:65]1[N:66]=[C:27]([CH:15]2[CH2:14][CH:13]([C:4]3[CH:5]=[CH:6][C:7]([CH2:8][C:9]([F:12])([F:10])[F:11])=[C:2]([F:1])[CH:3]=3)[CH2:18][N:17]([C:19]([N:21]3[CH2:22][CH2:23][S:24][CH2:25][CH2:26]3)=[O:20])[CH2:16]2)[O:28][N:64]=1)[CH3:69]

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 581165455-[3-Fluoro-4-(2,2,2-trifluoroethyl)phenyl]-1-(thiomorpholin-4-ylcarbonyl)piperidine-3-carboxylic acidHCID 76223295ethyl N-hydroxyimidocarbamate

Product 1

HCID 58116525{3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]piperidin-1-yl}-(thiomorpholin-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 400 mg (0.783 mmol, purity 85%) of the carboxylic acid from Example 79A in 10.6 ml of N,N-dimethylformamide were added, at room temperature, 357 mg (0.939 mmol) of HATU and 0.30 ml (1.72 mmol) of N,N-diisopropylethylamine, and the mixture was stirred for 30 min. Subsequently, the mixture was admixed with 118 mg (1.02 mmol, purity 90%) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] and stirred at room temperature overnight. The reaction solution was diluted with 11 ml of N,N-dimethylformamide and then stirred at 140° C. for 3 h. The reaction solution was purified directly by means of preparative HPLC. Yield: 111 mg (28% of theory)

Workup

  1. stirringstirred at 140° C. for 3 h
  2. customThe reaction solution was purified directly by means of preparative HPLC

Sources & evidence

ORD record
ord-244816eed22d420f8b1b852a80c8545f
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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