Potassium Carbonate → 6-(2,4-Difluorophenyl)-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamide

HRID 2044058Notes

Reaction equation

HRID 2044058 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[N:3]=1.[F:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.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:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[N:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 574896116-Chloro-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamide

Product 1

HCID 574896086-(2,4-Difluorophenyl)-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamideYield 35.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloro-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamide (40 mg, 0.107 mmol), 2,4-difluorophenylboronic acid (16.90 mg, 0.107 mmol), K2CO3 (29.6 mg, 0.214 mmol), and Pd(Ph3P)4 (12.36 mg, 10.70 μmol) in THF (2 mL) in a microwave vial was degassed by passing nitrogen through briefly. The vial was sealed and heated to 90° C. overnight. The reaction mixture was diluted with CH2Cl2, washed with satd. NaHCO3, water, and concentrated. The residue was purified by prep-HPLC. The product containing fractions were collected, basified by 1N NaOH, extracted with CH2Cl2, washed with water, concentrated to give 17 mg of 6-(2,4-difluorophenyl)-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamide as a yellow solid. LCMS: (M+H)+=452.08 1H NMR (400 MHz, CDCl3) δ ppm 10.80 (1H, s), 8.08 (1H, td, J=8.79, 6.59 Hz), 7.79-7.83 (1H, m), 7.77 (2H, d, J=8.35 Hz), 7.35 (2H, d, J=8.79 Hz), 7.23-7.27 (1H, m), 6.98-7.06 (1H, m), 6.93 (1H, ddd, J=11.42, 8.79, 2.64 Hz), 3.67 (4H, br. s.), 2.36-2.61 (4H, m), 2.33 (3H, s).

Workup

  1. customwas degassed
  2. customThe vial was sealed
  3. additionThe reaction mixture was diluted with CH2Cl2
  4. washwashed with satd
  5. concentrationNaHCO3, water, and concentrated
  6. customThe residue was purified by prep-HPLC
  7. additionThe product containing fractions
  8. customwere collected
  9. extractionextracted with CH2Cl2
  10. washwashed with water
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-b95a02c240be4661a54dee8c56f499c6
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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