Sodium Carbonate → 4-(4-Fluorophenyl)-7-(pyrimidin-5-ylmethyl)quinoline-2-carboxamide

HRID 922790Notes

Reaction equation

HRID 922790 reaction equation
Br[CH2:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[CH:8][C:9]([C:13]([NH2:15])=[O:14])=[N:10]2)=[CH:5][CH:4]=1.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>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>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:7]2[C:6]3[C:11](=[CH:12][C:3]([CH2:2][C:27]4[CH:28]=[N:23][CH:24]=[N:25][CH:26]=4)=[CH:4][CH:5]=3)[N:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 895440027-(Bromomethyl)-4-(4-fluorophenyl)-2-quinolinecarboxamide

Product 1

HCID 895440074-(4-Fluorophenyl)-7-(pyrimidin-5-ylmethyl)quinoline-2-carboxamideYield 8.2%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

Degassed DME (1237 μl)/Water (619 μl) was added to 7-(bromomethyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-1, 100 mg, 0.278 mmol), pyrimidin-5-ylboronic acid (41.4 mg, 0.334 mmol), Pd(PPh3)4 (16.09 mg, 0.014 mmol), and Na2CO3 (62.0 mg, 0.585 mmol). The reaction was heated at 100° C. in the microwave for 10 minutes. The reaction was quenched with water and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The crude material was purified by flash column chromatography (12 g SiO2, 0-100% EtOAc/hexanes) to afford impure product. The material was purified further by reverse phase HPLC (20×150 mm, Waters Sunfire, Solvent A=0.1% TFA/H2O, Solvent B=0.1% TFA/MeCN, 20 ml/min) to afford, after basic workup, 4-(4-fluorophenyl)-7-(pyrimidin-5-ylmethyl)quinoline-2-carboxamide (6-3, 8.16 mg, 8.18% yield) as a white solid. 1H NMR (500 MHz, CDCl3): δ 9.14 (s, 1H); 8.68 (s, 2H); 8.23 (s, 1H); 8.05 (s, 1H); 7.97 (s, 1H); 7.93 (d, J=8.7 Hz, 1H); 7.50 (dd, J=8.5, 5.4 Hz, 2H); 7.42 (dd, J=8.7, 1.8 Hz, 1H); 7.24 (t, J=8.5 Hz, 2H); 5.64 (s, 1H); 4.22 (s, 2H). LRMS m/z (M+H)+ 359.2 found, 359.4 required.

Workup

  1. customDegassed DME (1237 μl)/Water (619 μl)
  2. customThe reaction was quenched with water
  3. extractionthe mixture was extracted with ethyl acetate (×3)
  4. dry with materialThe combined organic fractions were dried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated under reduced pressure
  7. customThe crude material was purified by flash column chromatography (12 g SiO2, 0-100% EtOAc/hexanes)
  8. customto afford impure product
  9. customThe material was purified further by reverse phase HPLC (20×150 mm, Waters Sunfire, Solvent A=0.1% TFA/H2O, Solvent B=0.1% TFA/MeCN, 20 ml/min)
  10. customto afford

Sources & evidence

ORD record
ord-2e75ee61d6b04a639b41a00694190557
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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