4-Fluorobenzoyl chloride → N-[(4-{4-[(2-amino-6-phenylpyrimidin-4-yl)amino]phenoxy}pyridin-2-yl)methyl]4-fluorobenzamide

HRID 729918Notes

Reaction equation

HRID 729918 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:20]=[C:19]([NH2:29])[N:18]=3)=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1.[F:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=1>C1COCC1>[NH2:29][C:19]1[N:18]=[C:17]([NH:16][C:13]2[CH:12]=[CH:11][C:10]([O:9][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([CH2:2][NH:1][C:35](=[O:36])[C:34]4[CH:38]=[CH:39][C:31]([F:30])=[CH:32][CH:33]=4)[CH:8]=3)=[CH:15][CH:14]=2)[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:20]=1

Participants

4

Reactant 2

HCID 678794-Fluorobenzoyl chlorideHCID 57833404HCID 57833404, compound

Product 1

HCID 57833288N-[(4-{4-[(2-amino-6-phenylpyrimidin-4-yl)amino]phenoxy}pyridin-2-yl)methyl]4-fluorobenzamideYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N4-(4-{[2-(Aminomethyl)pyridin-4-yl]oxy}phenyl)-6-phenylpyrimidine-2,4-diamine (50 mg, 0.13 mmol, Example 39) and 4-fluorobenzoyl chloride (20.6 mg, 0.13 mmol) were suspended in THF (1 mL) and stirred at rt for 24 h. TLC and LC-MS indicated the reaction was completed. The mixture was extracted with EtOAc and washed with 1N aqueous sodium hydroxide solution (2×) and H2O (3×). The organic layer was dried and concentrated to give 68 mg of the crude product. The residue was purified by Prep-TLC (CH3OH:EtOAc=2:8) to obtain 38 mg (58%) of the title product as a yellowish oil. 1H NMR (CD3OD) δ 8.34 (d, 1H), 7.82 (m, 4H), 7.78 (d, 2H), 7.44 (m, 3H), 7.15 (t, 2H), 7.02 (d, 2H), 6.85 (d, 1H), 6.82 (s, 1H), 6.42 (s, 1H), 4.59 (s, 2H); MS ES 507 (M+H)+, calcd 507, RT=2.50 min; TLC (MeOH/EtOAc=20/80) Rf=0.57.

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. washwashed with 1N aqueous sodium hydroxide solution (2×) and H2O (3×)
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customto give 68 mg of the crude product
  6. customThe residue was purified by Prep-TLC (CH3OH:EtOAc=2:8)

Sources & evidence

ORD record
ord-6300ed0b77cf48af8adf4d2c7d74905b
Source dataset
uspto-grants-2009_09
Patent number
US07582645B2

Reaction notes

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