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

HRID 1803294Notes

Reaction equation

HRID 1803294 reaction equation
I.[F:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)[C:6]([O:15][CH3:16])=[CH:5][C:4]=1[NH:17][C:18](SC)=[NH:19].[Cl:22][CH2:23][CH2:24][CH2:25][CH2:26][CH:27]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]([F:42])([F:41])[F:40])=[CH:33][CH:32]=1)[C:28](O)=O.CN1CCOCC1.C(N(CC)C(C)C)(C)C.[NH2:59][NH2:60]>>[Cl:22][CH2:23][CH2:24][CH2:25][CH2:26][CH:27]([C:28]1[NH:60][N:59]=[C:18]([NH:17][C:4]2[CH:5]=[C:6]([O:15][CH3:16])[C:7]([N:9]3[CH:13]=[N:12][C:11]([CH3:14])=[N:10]3)=[CH:8][C:3]=2[F:2])[N:19]=1)[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]([F:40])([F:41])[F:42])=[CH:33][CH:32]=1

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 581101236-Chloro-2-(4-(2,2,2-trifluoroethoxy)phenyl)hexanoic acidHCID 178493242HCID 178493242, compound

Product 1

HCID 668583335-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Procedure

Methyl 2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenylcarbamimidothioate, hydroiodide (1.50 g, 3.54 mmol, from preparation B) and 6-chloro-2-(4-(2,2,2-trifluoroethoxy)phenyl)hexanoic acid (1.21 g, 3.72 mmol, from preparation AW) were coupled [N-methylmorpholine (1.95 mL, 17.7 mmol) was substituted for N,N-diisopropylethylamine] and then reacted with hydrazine (0.560 mL, 17.7 mmol) using a procedure analogous to Step A of Example 13. After an aqueous workup, 5-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine was obtained as a brown foamy solid. The crude product was used in the next step without purification. LC-MS (M+H)+ 568.5.

Sources & evidence

ORD record
ord-0ee2ce860207453980a14ad7b7fa60a8
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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