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

HRID 1479874Notes

Reaction equation

HRID 1479874 reaction equation
[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[CH3:2].CCOC(OC(OCC)=O)=O.[O:30]1[CH2:35][CH2:34][N:33]([C:36]2[CH:41]=[C:40]([CH2:42][NH2:43])[CH:39]=[C:38]([C:44]3[CH:49]=[CH:48][C:47]([C:50]([F:53])([F:52])[F:51])=[CH:46][CH:45]=3)[N:37]=2)[CH2:32][CH2:31]1>C1COCC1>[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([NH:43][CH2:42][C:40]1[CH:39]=[C:38]([C:44]2[CH:45]=[CH:46][C:47]([C:50]([F:53])([F:51])[F:52])=[CH:48][CH:49]=2)[N:37]=[C:36]([N:33]2[CH2:34][CH2:35][O:30][CH2:31][CH2:32]2)[CH:41]=1)=[O:7])[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 903842012-[Ethyl-(4-fluorophenyl)sulfonyl-amino]prop-2-enoic acidHCID 90390699[2-Morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine

Product 1

HCID 903902312-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4B (0.40 g, 1.46 mmol) in THF (20 mL) was added with DEPC (0.28 mL, 1.3 mol eq) and the mixture was stirred at room temperature several minutes. Then [2-morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27B (530 mg, 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, water was added to the residue that is extracted with EtOAc (3×30 mL) and washed with brine (1×40 mL). The separated organic phase was dried over Na2SO4, evaporated to dryness and the residue was purified by flash chromatography (6/4 EtOAc/Petroleum ether) to afford a white solid (95 mg) after crystallization from ethyl ether. Yield=12%. 1HNMR (DMSO, 200 MHz) δ 1.087 (t, 3H, J=7.8), 3.39 (q, 2H, J=7.6), 3.55 (m, 4H), 3.71 (m, 4H), 4.42 (d, 2H, J=6.2), 5.13 (s, 1H), 6.12 (s, 1H), 6.85 (s, 1H), 7.35 (s, 1H), 7.47 (t, 2H, J=8), 7.83-7.90 (m, 4H), 8.26 (d, 2H, J=8), 8.80 (bt, 1H). [M+1] 592.33 (C28H28F4N4O4S requires 592.60).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure, water
  3. additionwas added to the residue that
  4. extractionis extracted with EtOAc (3×30 mL)
  5. washwashed with brine (1×40 mL)
  6. dry with materialThe separated organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customthe residue was purified by flash chromatography (6/4 EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-e4708b418ba5452d9d9d754b0fab0fe0
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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