Triethylamine → tert-Butyl 4-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

HRID 705770Notes

Reaction equation

HRID 705770 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([NH2:12])=[O:11])#[CH:2].Cl[C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][C:26]=2[O:44][C:45]([F:48])([F:47])[F:46])[N:15]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.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>[NH2:12][C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:1]#[C:2][C:18]1[C:19]([C:20]([F:21])([F:23])[F:22])=[CH:14][N:15]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:32][CH2:33][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:35][CH2:36]3)=[CH:27][C:26]=2[O:44][C:45]([F:46])([F:47])[F:48])[N:17]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 533429972-(2-Ethynylphenyl)acetamideHCID 86675845Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

Product 1

HCID 86675846tert-Butyl 4-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a nitrogen de-gassed solution of 2-(2-ethynylphenyl)acetamide (I41) (0.029 g, 0.18 mmol) and tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate (I48) (0.082 g, 0.15 mmol) in dry DMF (4 mL) were added triethylamine (0.085 mL, 0.61 mmol), triphenylphosphine (6.0 mg, 0.023 mmol), trans-dichlorobis(triphenylphosphine)palladium (II) (0.011 g, 0.015 mmol) and Cu(I)I (4.0 mg, 0.023 mmol). The reaction mixture was heated under microwave irradiation at 120° C. for 20 minutes, concentrated to dryness in vacuo and purified by silica gel chromatography (12 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I49) (0.073 g, 73% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.11 (s, 1H), 8.74 (s, 1H), 7.58 (dd, J=7.7, 6.2 Hz, 2H), 7.53-7.47 (m, 1H), 7.42-7.27 (m, 5H), 6.99 (s, 1H), 4.14-4.03 (m, 2H), 3.67 (s, 2H), 2.87-2.72 (m, 3H), 1.79 (d, J=12.8 Hz, 2H), 1.50 (qd, J=12.5, 4.1 Hz, 2H), 1.42 (s, 9H). LCMS Method C: rt 6.63 min; m/z 564.0 [M-Boc+2H]+.

Workup

  1. concentrationconcentrated to dryness in vacuo
  2. custompurified by silica gel chromatography (12 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-3b075fa4aa804d5989be6582f08bf918
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

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