Triphenylphosphine → tert-Butyl 4-(4-((4-((2-(1-(methoxycarbonyl)cyclobutyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 592451Notes

Reaction equation

HRID 592451 reaction equation
[C:1]([C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][N:6]=[C:5]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[N:4]=1)#[CH:2].I[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]1([C:44]([O:46][CH3:47])=[O:45])[CH2:43][CH2:42][CH2:41]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.CCN(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:47][O:46][C:44]([C:40]1([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[C:2]#[C:1][C:3]2[C:8]([C:9]([F:10])([F:12])[F:11])=[CH:7][N:6]=[C:5]([NH:13][C:14]3[CH:15]=[CH:16][C:17]([CH:20]4[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]4)=[CH:18][CH:19]=3)[N:4]=2)[CH2:43][CH2:42][CH2:41]1)=[O:45]

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 86712324tert-Butyl 4-(4-((4-ethynyl-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 86712327Methyl 1-(2-iodophenyl)cyclobutanecarboxylate

Product 1

HCID 86712328tert-Butyl 4-(4-((4-((2-(1-(methoxycarbonyl)cyclobutyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A suspension of tert-butyl 4-(4-((4-ethynyl-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate A51 (169 mg, 0.380 mmol), methyl 1-(2-iodophenyl)cyclobutanecarboxylate A53 (100 mg, 0.316 mmol), PPh3 (8 mg, 0.03 mmol) and CuI (3 mg, 0.02 mmol) in DMF (3 mL) and Et3N (0.5 mL) was sonicated for 10 minutes before PdCl2(PPh3)2 (22 mg, 0.032 mmol) was added. The reaction mixture was irradiated in the microwave at 120° C. for 20 minutes, adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C. (column run twice)) to give the title compound A54 as a yellow oil (33 mg, 16%). LCMS-A: rt 7.919 min; m/z 635 [M+H]+.

Workup

  1. additionwas added
  2. customThe reaction mixture was irradiated in the microwave at 120° C. for 20 minutes
  3. custompurified
  4. customBiotage Isolera, 40 g SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-7b8eb5ee0e1344629d7225903d6c21f1
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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