Hydrazine → N-(5-(5-chloro-1-(4-fluorophenyl)pentyl)-1H-1,2,4-triazol-3-yl)-6-(4-chloro-1H-imidazol-1-yl)-5-methoxypyridin-3-amine

HRID 1803273Notes

Reaction equation

I.[Cl:2][C:3]1[N:4]=[CH:5][N:6]([C:8]2[N:13]=[CH:12][C:11]([NH:14][C:15](SC)=[NH:16])=[CH:10][C:9]=2[O:19][CH3:20])[CH:7]=1.[Cl:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[C:27](O)=O.[NH2:37][NH2:38]>>[Cl:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([C:27]1[NH:38][N:37]=[C:15]([NH:14][C:11]2[CH:12]=[N:13][C:8]([N:6]3[CH:7]=[C:3]([Cl:2])[N:4]=[CH:5]3)=[C:9]([O:19][CH3:20])[CH:10]=2)[N:16]=1)[C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1

Participants

Reactant 3

HCID 9321Hydrazine

HCID 581100396-Chloro-2-(4-fluorophenyl)hexanoic acid

HCID 178493243HCID 178493243, compound

Product 1

HCID 66858458N-(5-(5-chloro-1-(4-fluorophenyl)pentyl)-1H-1,2,4-triazol-3-yl)-6-(4-chloro-1H-imidazol-1-yl)-5-methoxypyridin-3-amineYield 47.8%

Procedure

Methyl 6-(4-chloro-1H-imidazol-1-yl)-5-methoxypyridin-3-ylcarbamimidothioate, hydroiodide (1.00 g, 2.349 mmol, from preparation O) and 6-chloro-2-(4-fluorophenyl)hexanoic acid (0.632 g, 2.58 mmol, from preparation AH) were coupled and then reacted with hydrazine (0.295 mL, 9.40 mmol) using a procedure analogous to Step A of Example 13. The crude product was purified using silica gel column chromatography (10-50, EtOAc/chloroform, linear gradient) to afford N-(5-(5-chloro-1-(4-fluorophenyl)pentyl)-1H-1,2,4-triazol-3-yl)-6-(4-chloro-1H-imidazol-1-yl)-5-methoxypyridin-3-amine (550 mg, 1.122 mmol, 47.7% yield). LC-MS (M+H)+ 490.2. After purification the product was still contaminated with a significant portion of HOBt. The impure product was used for subsequent chemistry without further purification.

Workup

customThe crude product was purified

Sources & evidence

ORD record: ord-710e176e94fe4751b0b7973de4202b6a
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349880B2

Reaction notes

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