4-Methylmorpholine → 5-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine
Reaction equation
I.[Cl:2][C:3]1[N:4]=[CH:5][N:6]([C:8]2[CH: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]([O:36][CH2:37][CH:38]([F:40])[F:39])=[CH:32][CH:31]=1)[C:27](O)=O.CN1CCOCC1.C(N(CC)C(C)C)(C)C.[NH2:57][NH2:58]>>[Cl:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([C:27]1[NH:58][N:57]=[C:15]([NH:14][C:11]2[CH:12]=[CH: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]([O:36][CH2:37][CH:38]([F:40])[F:39])=[CH:32][CH:31]=1Participants
6
Reactant 5
Product 1
Procedure
Methyl 4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylcarbamimidothioate, hydroiodide (1.108 g, 2.61 mmol, from preparation A) and 6-chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acid (1.0 g, 3.26 mmol, from preparation AX) were coupled [N-methylmorpholine (1.43 mL, 13.0 mmol) was substituted for N,N-diisopropylethylamine] and then reacted with hydrazine (0.410 mL, 13.1 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-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-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)+ 551.5.
Sources & evidence
- ORD record
- ord-6d937072fd48412785355872d3665e5c
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349880B2
Reaction notes
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