Cesium carbonate → HCID 25018142, compound

HRID 1878695Notes

Reaction equation

HRID 1878695 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](=[O:17])[N:12]([CH2:14][CH2:15][OH:16])[CH:13]=2)[CH:5]=[CH:6][CH:7]=1.Cl[C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=2)[N:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](=[O:17])[N:12]([CH2:14][CH2:15][O:16][C:19]3[C:28]4[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=4)[N:22]=[CH:21][CH:20]=3)[CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 106078294-Chloro-7-methoxyquinolineHCID 59843077HCID 59843077, compound

Product 1

HCID 25018142HCID 25018142, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

The crude 5-(3-fluorophenyl)-1-(2-hydroxyethyl)pyridin-2(1H)-one, 4-chloro-7-methoxyquinoline (107 mg, 553 μmol), cesium carbonate (191.2 mg, 587 μmol), palladium(II) acetate (24.6 mg, 110 μmol), and racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (50.2 mg, 126 μmol) were suspended in a microwave vial in toluene (3.0 ml) and sealed under argon. The tube was heated in a preheated oil bath (70° C.) and stirred for about 2 hours. The reaction was then cooled to room temperature and filtered through a silica gel filter [5:1 CH2Cl2/(2 N ammonia in MeOH)]. The filtrate was concentrated and purified on reverse phase HPLC (10%->95% MeCN/water with 0.1% TFA over 40 minutes on Shimatzu HPLC). The fractions with product were collected, concentrated, washed with Et2O, and then purified on a silica gel column (25:1->10:1 CH2Cl2/MeOH->10:1 CH2Cl2/2 N ammonia in MeOH) to afford the desired product (22.8 mg, 58.4 μmol, 13% yield over two steps). MS (ESI pos. ion) m/z (MH+): 391. Calc'd exact mass for C23H19FN2O3: 390. 1H NMR (400 MHz, CDCl3): 8.67 (d, J=5.0 Hz, 1H), 7.97 (d, J=9.0 Hz, 1H), 7.70 (d, J=2.0 Hz, 1H), 7.61 (dd, J=9.0 Hz, 2.0 Hz, 1H), 7.40-7.36 (m, 2H), 7.13 (d, J=8.0 Hz, 1H), 7.07-7.02 (m, 3H), 6.70 (d, J=9.0 Hz, 1H), 6.67 (d, J=5.2 Hz, 1H), 4.62-4.54 (m, 4H), 3.94 (s, 3H).

Workup

  1. customsealed under argon
  2. temperatureThe reaction was then cooled to room temperature
  3. filtrationfiltered through a silica gel
  4. filtrationfilter [5:1 CH2Cl2/(2 N ammonia in MeOH)]
  5. concentrationThe filtrate was concentrated
  6. custompurified on reverse phase HPLC (10%->95% MeCN/water with 0.1% TFA over 40 minutes on Shimatzu HPLC)
  7. customThe fractions with product were collected
  8. concentrationconcentrated
  9. washwashed with Et2O
  10. custompurified on a silica gel column (25:1->10:1 CH2Cl2/MeOH->10:1 CH2Cl2/2 N ammonia in MeOH)

Sources & evidence

ORD record
ord-a8bc68f6934b4916ba214e13f84b52f5
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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