Pyridine → HCID 178510423, compound

HRID 408943Notes

Reaction equation

HRID 408943 reaction equation
[C:1]1([C:7]2[CH:12]=[C:11]([CH:13]([CH2:16][OH:17])[CH2:14][OH:15])[CH:10]=[CH:9][C:8]=2[NH:18][C:19]([C:21]2[NH:22][CH:23]=[C:24]([C:26]#[N:27])[N:25]=2)=[O:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.N1C=CC=CC=1.Cl[C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1.C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([CH:13]3[CH2:14][O:15][C:35](=[O:37])[O:17][CH2:16]3)[CH:10]=[CH:9][C:8]=2[NH:18][C:19]([C:21]2[NH:22][CH:23]=[C:24]([C:26]#[N:27])[N:25]=2)=[O:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 94429TriphosgeneHCID 178510428HCID 178510428, compound

Product 1

HCID 178510423HCID 178510423, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(2-hydroxy-1-hydroxymethyl-ethyl)-phenyl]-amide (as prepared in the previous step, 5.4 mg, 0.015 mmol) and pyridine (3.0 μL, 0.037 mmol) in 0.5 mL of THF at −78° C. was added a solution of triphosgene (1.8 mg, 0.0061 mmol) in 0.5 mL of DCM. The resulting mixture was warmed to RT and continued to stir for 1 h under Ar. Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-2% MeOH-DCM) gave 2.8 mg (48%) of the title compound as a white solid: 1H-NMR (CD3OD; 400 MHz): δ 8.01 (s, 1H), 7.66 (dd, 1H, J=8.6, 2.3 Hz), 7.59 (d, 1H, J=2.3 Hz), 7.29 (d, 1H, J=8.6 Hz), 5.66 (m, 1H), 4.65 (dd, 2H, J=10.9, 10.9 Hz), 4.45 (dd, 2H, J=10.9, 4.9 Hz), 3.72 (m, 1H), 2.24 (m, 4H), 1.70-1.88 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C21H20N4O4, 393.2 (M+H). found 393.1.

Workup

  1. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-43bf583be1864f9bb0bc0527338fffdf
Source dataset
uspto-grants-2014_06
Patent number
US08759347B2

Reaction notes

Loading…