4-Fluorophenylboronic acid → 7-[(2,5-Dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carbonitrile

HRID 922757Notes

Reaction equation

HRID 922757 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([CH2:27][N:28]3[C:32](=[O:33])[CH2:31][CH2:30][C:29]3=[O:34])=[CH:24][CH:25]=2)[N:20]=[C:19]([C:35]#[N:36])[CH:18]=1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:33]=[C:32]1[CH2:31][CH2:30][C:29](=[O:34])[N:28]1[CH2:27][C:23]1[CH:22]=[C:21]2[C:26]([C:17]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[CH:18][C:19]([C:35]#[N:36])=[N:20]2)=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 895436784-Chloro-7-((2,5-dioxopyrrolidin-1-yl)methyl)quinoline-2-carbonitrile

Product 1

HCID 715666687-[(2,5-Dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a room temperature solution of 4-fluorophenylboronic acid (5.96 g, 42.6 mmol, 1.2 equiv.) in dioxane:water (10:1, 177 mL, 0.2 M) was added sodium bicarbonate (5.96 g, 71.0 mmol, 2.0 equiv.), 4-chloro-7-[(2,5-dioxopyrrolidin-1-yl)methyl]quinoline-2-carbonitrile (2-5, 10.6 g, 35.5 mmol), and Pd(PPh3)4 (4.1 g, 3.55 mmol, 0.1 equiv.). The resulting mixture was warmed to 100° C. for 4 hr. The reaction was then cooled to 0° C. and a precipitate formed. The solids were then collected by vacuum filtration and washed with water and cold acetonitrile to afford 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carbonitrile (2-6) which was taken to the next step without further purification. 1H NMR (400 MHz, CDCl3): δ 8.115 (d, J=1.10 Hz, 1H); 7.897 (d, J=8.79 Hz, 1H); 7.655 (dd, J1=8.79 Hz, J2=1.83 Hz, 1H); 7.603 (s, 1H); 7.439-7.475 (m, 2H); 7.243-7.286 (m, 2H); 4.909 (s, 2H); 2.796 (s, 4H). LRMS m/z (M+H)+ 360.3 found, 360.1 required.

Workup

  1. temperatureThe reaction was then cooled to 0° C.
  2. customa precipitate formed
  3. filtrationThe solids were then collected by vacuum filtration
  4. washwashed with water and cold acetonitrile

Sources & evidence

ORD record
ord-ea1f76d3f5274d3ca619548e0163f7e6
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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