4-Methylmorpholine → HCID 178461365, compound

HRID 501279Notes

Reaction equation

HRID 501279 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[CH:4]=[CH:5][C:6]2[C:10]([N:11]3[CH2:16][CH2:15][N:14]([CH2:17][C@@H:18]4[CH2:20][C@H:19]4[C:21]([OH:23])=O)[CH2:13][CH2:12]3)=[CH:9][S:8][C:7]=2[CH:24]=1.C(OC(C(=NOC(N(C)C)=[N+](C)C)C#N)=O)C.F[B-](F)(F)F.CN1CCOCC1.[CH3:56][C@H:57]1[CH2:62][CH2:61][C@H:60]([NH2:63])[CH2:59][CH2:58]1>CN(C=O)C>[CH3:56][C@H:57]1[CH2:62][CH2:61][C@H:60]([NH:63][C:21]([C@@H:19]2[CH2:20][C@H:18]2[CH2:17][N:14]2[CH2:15][CH2:16][N:11]([C:10]3[C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:25])[F:26])=[CH:24][C:7]=4[S:8][CH:9]=3)[CH2:12][CH2:13]2)=[O:23])[CH2:59][CH2:58]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 18436982trans-2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-ylmethyl]-cyclopropanecarboxylic acidHCID 178461305HCID 178461305, compound

Product 1

HCID 178461365HCID 178461365, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Stir a solution of trans-2-[4-(6-trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-ylmethyl]-cyclopropanecarboxylic acid (Example 7a) (1.99 g, 5.0 mmol), and O-[(ethoxycarbonyl)-cyanomethylenamino]-N,N,N′,N′-tetramethyluronium-tetrafluoroborate (TOTU, 2.05 g, 6.3 mmol) in DMF (50 mL) at 20° C. for 0.5 h. Add N-methylmorpholine (0.58 mL, 5.3 mmol), after which add trans-4-methylcyclohexylamine (1.13 g, 10 mmol), and stir the reaction for 5 h. Concentrate the reaction under reduced pressure to obtain an oil. Purify by column chromatography over silica gel (EtOAc(heptane/methanol/triethylamine, 20:20:1:1) to obtain 1.86, (76%) of colorless crystals LC/MS, m/z=480 (M+H)+.

Workup

  1. customthe reaction for 5 h
  2. concentrationConcentrate
  3. customthe reaction under reduced pressure
  4. customto obtain an oil
  5. customPurify by column chromatography over silica gel (EtOAc(heptane/methanol/triethylamine, 20:20:1:1)

Sources & evidence

ORD record
ord-367c8c0699754967ad0797c9f9fb01f4
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

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