Acetic Acid → HCID 11511695, compound

HRID 1785949Notes

Reaction equation

HRID 1785949 reaction equation
Br.[NH2:2][C@H:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([C:13]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH:24]([CH3:26])[CH3:25])[N:19]=[CH:18]3)=[O:14])[C@@H:5]([CH3:27])[CH2:4]1.[Cl:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.C(N(CC)CC)C.[CH3:45][C:46](O)=[O:47]>[Pd].ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.N1C=CC=CC=1>[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([N:2]([C@H:3]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([CH:24]([CH3:26])[CH3:25])[N:19]=[CH:18]4)=[O:14])[C@@H:5]([CH3:27])[CH2:4]2)[C:46](=[O:47])[CH3:45])=[CH:31][CH:30]=1

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 8471TriethylamineHCID 742994-Chlorophenylboronic acidHCID 68925263HCID 68925263, compound

Product 1

HCID 11511695HCID 11511695, compound

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 23938PalladiumCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide was prepared following general procedure G, substituting 1-Isopropyl-1H-indazole-5-carbonyl chloride for 4-fluorobenzoyl chloride. (1-Isopropyl-1H-indazole-5-carbonyl chloride was prepared in three steps from 1H-Indazole-5-carboxylic acid ethyl ester. 1H-Indazole-5-carboxylic acid ethyl ester was alkylated using 2-bromopropane in presence of sodium hydride in DMF at room temperature to yield the desired 1-isopropyl-1H-indazole-5-carboxylic acid ethyl ester. Ester hydrolysis using 1N sodium hydroxide in ethanol at 80° C. gave 1-Isopropyl-1H-indazole-5-carboxylic acid and subsequent treatment of this carboxylic acid with oxalyl chloride and catalytic DMF afforded 1-isopropyl-1H-indazole-5-carbonyl chloride in decent yield). The rest of the procedures were followed as indicated in general procedure G to afford (2S,4R)-N-(4-Chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide. (The first exception being in the deprotection of the benzyloxycarbonyl group by treatment with 30% HBr in AcOH substituting for palladium on carbon (10%) and the other in the step of N-arylation of (2S,4R)-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(1-isopropyl-1H-indazol-5-yl)-methanone with 4-chlorophenylboronic acid, in presence of copper acetate, triethylamine was substituted for pyridine, and the reaction was carried out in dichloromethane at room temperature to afford the (2S,4R)-N-(4-chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide).

Sources & evidence

ORD record
ord-94f6cd23ee694e4c95608c31b58a9530
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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