3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}benzonitrile → HCID 178432871, compound

HRID 1875230Notes

Reaction equation

HRID 1875230 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:19])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Cl:20][C:21]1[N:22]=[C:23]([CH3:29])[NH:24][C:25]=1[C:26](O)=[O:27]>>[Cl:20][C:21]1[N:22]=[C:23]([CH3:29])[NH:24][C:25]=1[C:26]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[CH:17][CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:19])=[O:27]

Participants

3

Reactant 2

HCID 687218663-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}benzonitrileHCID 178432882HCID 178432882, compound

Product 1

HCID 178432871HCID 178432871, compoundYield 40.1%

Procedure

A solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.20 g, 0.56 mmol), sodium formate (0.057 g, 0.84 mmol) and Pd(Ph3P)4 (0.032 g, 0.028 mmol) in DMF (1.13 ml) was heated at 100° C. for 6 h. Water was added and the mixture was extracted with EtOAc. The organic phase was dried (Na2SO4), filtered, and dried to afford 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}benzonitrile, which was used without further purification. The above amine (0.28 mmol) and 4-chloro-2-methyl-1H-imidazole-5-carboxylic acid (0.040 g, 0.25 mmol) were employed in a similar process described herein to prepare the title compound (0.042 g, 40%) as a white solid after purification by Reverse-Phase HPLC (water:acetonitrile with 0.1% TFA) followed by neutralization. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.89 (br. s., 1H), 7.32-7.45 (m, 2H), 7.12-7.31 (m, 4 H), 7.08 (s, 1H), 4.70 (d, J=5.91 Hz, 2H), 2.37 (s, 3H). ES-LCMS: m/z 419.0, 421.0 (M+1).

Workup

  1. customwas used without further purification

Sources & evidence

ORD record
ord-497d94787843460f9a1629cb06fdf401
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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