Trifluoroacetic acid → HCID 86650670, compound

HRID 1969470Notes

Reaction equation

HRID 1969470 reaction equation
FC(F)(F)C(O)=O.[O:8]=[C:9]1[C:13](N[C@@H](C2C=CC=CC=2)C)=[CH:12][C@H:11]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:33])([F:32])[F:31])[CH:24]=2)[N:10]1[C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][CH:35]=1.O=C1C(=O)C[C@H](C2C=CC=C(OC(F)(F)F)C=2)N1C1C=CC(C#N)=CC=1.[CH3:68][C:69]([NH2:81])([C:71]1[CH:76]=[CH:75][CH:74]=[C:73]([C:77]([F:80])([F:79])[F:78])[N:72]=1)[CH3:70]>ClCCl.O>[CH3:70][C:69]([NH:81][C:13]1[C:9](=[O:8])[N:10]([C:34]2[CH:35]=[CH:36][C:37]([C:38]#[N:39])=[CH:40][CH:41]=2)[C@@H:11]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:31])([F:33])[F:32])[CH:24]=2)[CH:12]=1)([C:71]1[CH:76]=[CH:75][CH:74]=[C:73]([C:77]([F:79])([F:80])[F:78])[N:72]=1)[CH3:68]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 573469902-[6-(Trifluoromethyl)pyridin-2-yl]propan-2-amineHCID 66909253HCID 66909253, compoundHCID 66937059HCID 66937059, compound

Product 1

HCID 86650670HCID 86650670, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Add trifluoroacetic acid (2.00 mL, 26.43 mmol) to a biphasic mixture of 4-[(R)-2-oxo-3-((R)-1-phenyl-ethylamino)-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile) in dichloromethane (12 mL) and water (4.9 mL). Stir at ambient temperature for 2 hours. Observe significant formation of 4-[(R)-2,3-dioxo-5-(3-trifluoromethoxy-phenyl)-pyrrolidin-1-yl]-benzonitrile (LC-MS ESI m/z: 361 (M+H)+, Tr=2.34 min., method 2. Wash the reaction mixture with water. Filter the organic phase through sodium sulfate and add 1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamine (1.30 g, 6.35 mmol). Heat to reflux temperature for 18 hours. Partially concentrate reaction mixture and place on a silica gel chromatography column. Purify by silica gel chromatography (25% ethyl acetate-hexane) to obtain 4-[(R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-2-oxo-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile (1.06 g, 37%). 1H NMR (400 MHz, CDCl3) δ 7.71 (t, J=7.9 Hz, 1H), 7.64-7.61 (m, 2H), 7.59 (d, J=7.9 Hz, 1H), 7.53-7.44 (m, 4H), 7.26-7.24 (m, 1H), 7.04-6.96 (m, 2H), 6.80 (s, 1H), 5.38 (d, J=2.6 Hz, 1H), 4.99-4.97 (m, 1H), 4.69 (d, J=2.6 Hz, 1H), 1.65 (d, J=7.5 Hz, 6H).

Workup

  1. custom361 (M+H)+, Tr=2.34 min., method 2
  2. washWash the reaction mixture with water
  3. filtrationFilter the organic phase through sodium sulfate
  4. temperatureHeat
  5. temperatureto reflux temperature for 18 hours
  6. customPartially concentrate reaction mixture and place on a silica gel chromatography column
  7. customPurify by silica gel chromatography (25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-3c14cf3204054fe4b575d11e6bd959c0
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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