Diethyl Pyrocarbonate → 2-[(4-chlorophenyl)sulfonyl-methyl-amino]-N-[[2-morpholino-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]prop-2-enamide

HRID 1479831Notes

Reaction equation

HRID 1479831 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:17])[C:12](=[CH2:16])[C:13]([OH:15])=O)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCOC(OC(OCC)=O)=O.[O:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[C:39]([CH2:41][NH2:42])[CH:38]=[C:37]([C:43]3[CH:48]=[CH:47][C:46]([O:49][C:50]([F:53])([F:52])[F:51])=[CH:45][CH:44]=3)[N:36]=2)[CH2:31][CH2:30]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH3:17])[C:12](=[CH2:16])[C:13]([NH:42][CH2:41][C:39]2[CH:38]=[C:37]([C:43]3[CH:48]=[CH:47][C:46]([O:49][C:50]([F:53])([F:51])[F:52])=[CH:45][CH:44]=3)[N:36]=[C:35]([N:32]3[CH2:31][CH2:30][O:29][CH2:34][CH2:33]3)[CH:40]=2)=[O:15])(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 1317365842-[(4-Chlorophenyl)sulfonyl-methyl-amino]prop-2-enoic acidHCID 131736588[2-Morpholino-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine

Product 1

HCID 783205282-[(4-chlorophenyl)sulfonyl-methyl-amino]-N-[[2-morpholino-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4C (0.40 g, 1.45 mmol) in THF (25 mL) was added with DEPC (0.28 mL, 1.3 mol eq) and the mixture was stirred at room temperature for about 5 minutes. Then [2-morpholino-6-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine 27D (0.56 g, 1.1 mol eq) and a catalytic amount of TEA were added, then the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue was suspended in EtOAc and washed with water and brine. After drying over Na2SO4, the separated organic phase was evaporated under reduced pressure and the residue was purified by flash chromatography (7:3 EtOAc:Petroleum ether) to afford a pale yellow solid (0.24 g) after crystallization from a mixture of diethyl ether/petroleum ether. Yield=36%, 1HNMR (DMSO, 200 MHz) δ 2.95 (s, 3H), 3.55 (m, 4H), 3.70 (m, 4H), 4.40 (d, 2H, J=6), 5.12 (s, 1H), 5.87 (s, 1H), 6.82 (s, 1H), 7.29 (s, 1H), 7.43 (d, 2H, J=8.2), 7.83-7.74 (m, 4H), 8.17 (d, 2H, J=8), 8.86 (t, 1H); [M+1] 611.03 (C27H26ClF3N4O5S requires 610.13).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. washwashed with water and brine
  4. dry with materialAfter drying over Na2SO4
  5. customthe separated organic phase was evaporated under reduced pressure
  6. customthe residue was purified by flash chromatography (7:3 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-24732f84bc954206b22527c184aa2bc7
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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