Tetrafluoroborate → tert-Butyl 4-(5-((4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

HRID 592487Notes

Reaction equation

HRID 592487 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[N:17][CH:18]=2)[N:3]=1.[C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]1([C:43]([NH2:45])=[O:44])[CH2:42][CH2:41]1)#[CH:33].F[B-](F)(F)F.CCN(C(C)C)C(C)C>[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.O1CCOCC1>[C:43]([C:40]1([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[C:32]#[C:33][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]4)=[N:17][CH:18]=3)[N:3]=2)[CH2:41][CH2:42]1)(=[O:44])[NH2:45]

Participants

8

Reactant 4

HCID 26255TetrafluoroborateHCID 81531DiisopropylethylamineHCID 86712273tert-Butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylateHCID 867122761-(2-Ethynylphenyl)cyclopropanecarboxamide

Product 1

HCID 86712348tert-Butyl 4-(5-((4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of tert-butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate A70 (0.208 g, 0.453 mmol), 1-(2-ethynylphenyl)cyclopropanecarboxamide K6 (0.079 g, 0.42 mmol), CuI (0.003 g, 0.02 mmol), PdCl2(PPh3)2 (0.017 g, 0.024 mmol) and t-Bu3PH.BF4 (0.009 g, 0.03 mmol) under a nitrogen atmosphere was added dioxane (6.0 mL) and DIPEA (0.23 mL, 1.3 mmol). The mixture was stirred at 85° C. for 4 hours and then concentrated under reduced pressure. Purification by silica gel column chromatography (Biotage Isolera, 0-100% EtOAc in Petroleum Benzine 40-60° C., 0-20% MeOH in EtOAc) gave the title compound A78 (0.118 g, 46%). LCMS-D: rt 3.645 min; m/z 607.4 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customPurification by silica gel column chromatography (Biotage Isolera, 0-100% EtOAc in Petroleum Benzine 40-60° C., 0-20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-c099549b5ef34a8cadaad87f7eca9b3c
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

Loading…