Dimethylformamide → HCID 178432880, compound

HRID 1875179Notes

Reaction equation

HRID 1875179 reaction equation
Br[C:2]1[C:3]([Cl:30])=[C:4]([O:20][C:21]2[CH:26]=[C:25]([C:27]#[N:28])[CH:24]=[C:23]([Cl:29])[CH:22]=2)[C:5]([F:19])=[C:6]([CH2:8][NH:9][C:10]([C:12]2[NH:16][C:15]([CH3:17])=[N:14][C:13]=2[Cl:18])=[O:11])[CH:7]=1.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32].[CH3:38][N:39](C=O)C>[C-]#N.[Zn+2].[C-]#N.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:34][C:33]([F:36])([F:35])[C:31]([OH:37])=[O:32].[Cl:18][C:13]1[N:14]=[C:15]([CH3:17])[NH:16][C:12]=1[C:10]([NH:9][CH2:8][C:6]1[CH:7]=[C:2]([C:38]#[N:39])[C:3]([Cl:30])=[C:4]([O:20][C:21]2[CH:26]=[C:25]([C:27]#[N:28])[CH:24]=[C:23]([Cl:29])[CH:22]=2)[C:5]=1[F:19])=[O:11]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acidHCID 178432866HCID 178432866, compound

Product 1

HCID 178432880HCID 178432880, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A solution of N-({5-bromo-4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-4-chloro-2-methyl-1H-imidazole-5-carboxamide (70 mg, 0.131 mmol), zinc cyanide (7.72 mg, 0.066 mmol) and tetrakis(triphenylphosphine)palladium(0) (30.4 mg, 0.026 mmol) in DMF (1.5 ml) was irradiated for 35 minutes at 130° C. in a microwave reactor. The reaction mixture was purified via reverse phase HPLC to give 4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-5-cyano-2-fluorophenyl}methyl)-2-methyl-1H-imidazole-5-carboxamide trifluoroacetate (5.8 mg, 9.79 μmol, 7% yield) as the TFA salt. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.79 (d, 1H), 7.58 (s, 1H), 7.37 (s, 1H), 7.32 (s, 1H), 4.62 (s, 2H), 2.33 (s, 3H). LC-MS (ES+) m/z 477.95, [M+H].

Workup

  1. customThe reaction mixture was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-5fa332e6cc5d4d54bb60990c25281d70
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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