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

HRID 1634118Notes

Reaction equation

HRID 1634118 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][CH3:14])=[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+]>CC(O)=O.CO>[CH2:13]([C:12]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][CH2:24][C:23]3[C:26]([F:30])=[CH:27][CH:28]=[CH:29][C:22]=3[Cl:21])=[CH:3][CH:4]=2)[N:9]=[C:10]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[CH:11]=1)[CH3:14]

Participants

5

Reactant 3

HCID 678472-Chloro-6-fluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 186770941-(4-Aminophenyl)-3-(3-pyridyl)-5-ethylpyrazole

Product 1

HCID 18677149[4-(5-Ethyl-3-pyridin-3-yl-pyrazol-1-yl)phenyl]-(2-chloro-6-fluorobenzyl)amine

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent

Procedure

To a stirred solution of 1(4-aminophenyl)-3-(3-pyridyl)-5-ethylpyrazole (300 mg, 1.14 mmol) and 2-chloro-6-fluorobenzaldehyde (360 mg, 2.27 mmol) in 5% HOAc/MeOH (6 mL) at room temperature under argon was added sodium cyanoborohydride (180 mg, 2.86 mmol). The reaction mixture was stirred at room temperature for 4 h and then concentrated, diluted with water, extracted into ethyl acetate and washed with brine. The residue obtained on concentration was chromatographed on silica gel (eluant, gradient of 25-50% EtOAc in hexane) to provide the title compound as an oil which solidified on trituration with ether/petroleum (152 mg, 32%). m.p. 123-5° C. NMR (CDCl3, 400 MHz): 9.1 (s, 1H); 8.6 (br, 1H); 8.2 (br, 1H); 7.4-7.2 (overlapping m, 5H), 7.05 (m, 1H), 6.8 (d, 2H), 6.6 (s, 1H), 4.6 (s, 2H), 4.4 (br, 1H), 2.7 (q, 2H), 1.2 (t, 3H).

Workup

  1. concentrationconcentrated
  2. additiondiluted with water
  3. extractionextracted into ethyl acetate
  4. washwashed with brine
  5. customThe residue obtained on concentration
  6. customwas chromatographed on silica gel (eluant, gradient of 25-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-658c0f17102f496cb17bed5f437223b5
Source dataset
uspto-grants-2003_01
Patent number
US06506747B1

Reaction notes

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