2-Fluoro-alpha-methylbenzenemethanol → (4,4-Difluoro-piperidin-1-yl)-[1-[1-(2-fluoro-phenyl)-ethyl]-5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-methanone

HRID 1820440Notes

Reaction equation

HRID 1820440 reaction equation
[Cl-].C(C[P+](C)(C)C)#N.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH:26](O)[CH3:27].[F:29][C:30]1([F:58])[CH2:35][CH2:34][N:33]([C:36]([C:38]2[NH:39][C:40]3[C:45]([CH:46]=2)=[CH:44][C:43]([C:47]([N:49]2[CH2:54][CH2:53][N:52]([CH:55]([CH3:57])[CH3:56])[CH2:51][CH2:50]2)=[O:48])=[CH:42][CH:41]=3)=[O:37])[CH2:32][CH2:31]1>C1(C)C=CC=CC=1>[F:58][C:30]1([F:29])[CH2:35][CH2:34][N:33]([C:36]([C:38]2[N:39]([CH:26]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[F:19])[CH3:27])[C:40]3[C:45]([CH:46]=2)=[CH:44][C:43]([C:47]([N:49]2[CH2:50][CH2:51][N:52]([CH:55]([CH3:56])[CH3:57])[CH2:53][CH2:54]2)=[O:48])=[CH:42][CH:41]=3)=[O:37])[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 1230662-Fluoro-alpha-methylbenzenemethanolHCID 3251421Potassium bis(trimethylsilyl)amideHCID 57431663(Cyanomethyl)trimethylphosphonium chlorideHCID 68680853(4,4-Difluoro-piperidin-1-yl)-[5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-methanone

Product 1

HCID 68681415(4,4-Difluoro-piperidin-1-yl)-[1-[1-(2-fluoro-phenyl)-ethyl]-5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-methanoneYield 15%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The title compound was synthesized in analogy to example 74, from (cyanomethyl)-trimethylphosphonium chloride (prepared according to Tetrahedron Lett. 1996, 37 (14), 2459-62), potassium bis(trimethylsilyl)amide, 1-(2-fluorophenyl)ethanol and (4,4-difluoro-piperidin-1-yl)-[5-(4-isopropyl-piperazine-1-carbonyl)-1H-indol-2-yl]-methanone (example 32) in toluene, to give the desired product as a light brown foam (15%).

Sources & evidence

ORD record
ord-75d08c0f11be4fcebbee6fab60088d99
Source dataset
uspto-grants-2009_10
Patent number
US07601711B2

Reaction notes

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