4-Methylmorpholine → 5-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

HRID 1803296Notes

Reaction equation

HRID 1803296 reaction equation
I.[F:2][C:3]1[CH:4]=[C:5]([NH:15][C:16](SC)=[NH:17])[CH:6]=[CH:7][C:8]=1[N:9]1[C:13]([CH3:14])=[N:12][CH:11]=[N:10]1.[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH:37]([F:39])[F:38])=[CH:31][CH:30]=1)[C:26](O)=O.CN1CCOCC1.C(N(CC)C(C)C)(C)C.[NH2:56][NH2:57]>>[Cl:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]([C:26]1[NH:57][N:56]=[C:16]([NH:15][C:5]2[CH:6]=[CH:7][C:8]([N:9]3[C:13]([CH3:14])=[N:12][CH:11]=[N:10]3)=[C:3]([F:2])[CH:4]=2)[N:17]=1)[C:29]1[CH:30]=[CH:31][C:32]([O:35][CH2:36][CH:37]([F:38])[F:39])=[CH:33][CH:34]=1

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 581101806-Chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acidHCID 178504012HCID 178504012, compound

Product 1

HCID 866499345-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Procedure

Methyl 3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenylcarbamimidothioate, hydroiodide (1.22 g, 3.10 mmol, from preparation C) and 6-chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acid (1.0 g, 3.26 mmol, from preparation AX) were coupled [N-methylmorpholine (1.71 mL, 15.5 mmol) was substituted for N,N-diisopropylethylamine] and then reacted with hydrazine (0.490 mL, 15.5 mmol) using a procedure analogous to Step A of Example 13. After an aqueous workup, 5-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine was obtained as a brown solid. The crude product was used in the next step without purification. LC-MS (M+H)+ 520.5.

Sources & evidence

ORD record
ord-4bb00e45b4d74f049412ca198261621b
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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