4-Methylmorpholine → 5-(5-chloro-1-(4-(trifluoromethoxy)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 1803330Notes

Reaction equation

HRID 1803330 reaction equation
Br.[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](SCC=C)=[NH:19].[Cl:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]([C:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]([F:43])([F:42])[F:41])=[CH:35][CH:34]=1)[C:30](O)=O.CN1CCOCC1.C(N(CC)C(C)C)(C)C.[NH2:60][NH2:61]>>[Cl:24][CH2:25][CH2:26][CH2:27][CH2:28][CH:29]([C:30]1[NH:61][N:60]=[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:33]1[CH:38]=[CH:37][C:36]([O:39][C:40]([F:41])([F:42])[F:43])=[CH:35][CH:34]=1

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 581101836-Chloro-2-(4-(trifluoromethoxy)phenyl)hexanoic acidHCID 178419557allyl 2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenylcarbamimidothioate, hydrobromide

Product 1

HCID 668588375-(5-chloro-1-(4-(trifluoromethoxy)phenyl)pentyl)-N-(2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amineYield 29.1%

Procedure

Allyl 2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenylcarbamimidothioate, hydrobromide (1.42 g, 3.54 mmol, from preparation U) and 6-chloro-2-(4-(trifluoromethoxy)phenyl)hexanoic acid (1.375 g, 4.43 mmol, from preparation AY) were coupled [N-methylmorpholine (2.00 mL, 17.7 mmol) was substituted for N,N-diisopropylethylamine] and then reacted with hydrazine (0.556 mL, 17.7 mmol) using a procedure analogous to Step A of Example 13. After purification by silica gel column chromatography, 5-(5-chloro-1-(4-(trifluoromethoxy)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 (570 mg, 1.03 mmol, 29% yield) as a foamy solid. LC-MS (M+H)+ 554.3.

Sources & evidence

ORD record
ord-16b91ea350e44304b2c43b004a923b0e
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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