2-Chloro-6-fluorobenzaldehyde → (2-Chloro-6-fluorobenzyl)-[4-(5-cyano-3-pyridin-3-yl-pyrazol-1-yl)phenyl]amine

HRID 1634113Notes

Reaction equation

HRID 1634113 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]#[N:14])=[CH:11][C:10]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)=[N:9]2)=[CH:4][CH:3]=1.[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:23]=1[CH:24]=O.C([BH3-])#N.[Na+]>C(O)(=O)C.CO>[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:23]=1[CH2:24][NH:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]#[N:14])=[CH:11][C:10]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)=[N:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 678472-Chloro-6-fluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 186771061-(4-Aminophenyl)-3-(3-pyridyl)-5-cyanopyrazole

Product 1

HCID 18677101(2-Chloro-6-fluorobenzyl)-[4-(5-cyano-3-pyridin-3-yl-pyrazol-1-yl)phenyl]amineYield 51%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a stirred solution of 1-(4-aminophenyl)-3-(3-pyridyl)-5-cyanopyrazole (130 mg, 0.5 mmol) in acetic acid (2 mL) and MeOH (6 mL) at room temperature was added 2-chloro-6-fluorobenzaldehyde (79 mg, 0.5 mmol), followed by sodium cyanoborohydride (79 mg, 1.25 mmol). The reaction mixture was stirred at room temperature for 16 h and then concentrated under a stream of nitrogen. The residue was diluted with water, extracted into ethyl acetate, washed with sodium bicarbonate solution and water, and dried (MgSO4). The residue obtained on concentration was flash chromatographed on silica gel (eluent, gradient of 20-30% EtOAc in CH2Cl2) to provide the title compound (103 mg, 51%). NMR (CDCl3, 400 MHz): 9.1 (s, 1H); 8.7 (br, 1H); 8.3 (d, 1H); 7.6-7.5 (overlapping m, 3H), 7.6-7.5 (overlapping m, 4H), 7.05 (m, 1H); 6.9 (d, 2H), 4.6 (s, 2H).

Workup

  1. concentrationconcentrated under a stream of nitrogen
  2. additionThe residue was diluted with water
  3. extractionextracted into ethyl acetate
  4. washwashed with sodium bicarbonate solution and water
  5. dry with materialdried (MgSO4)
  6. customThe residue obtained on concentration
  7. customchromatographed on silica gel (eluent, gradient of 20-30% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-c8484f914fac497da40d1217b4385a87
Source dataset
uspto-grants-2003_01
Patent number
US06506747B1

Reaction notes

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