Triethylamine → tert-Butyl 3-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

HRID 592369Notes

Reaction equation

HRID 592369 reaction equation
[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]#[C:15][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34]4)=[CH:29][CH:28]=3)[N:17]=2)[CH2:7][CH2:6]1)=[O:4].CCN(CC)CC.[H][H]>CN(C=O)C.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[CH2:14][CH2:15][C:16]2[C:21]([C:22]([F:23])([F:25])[F:24])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([CH:33]4[CH2:34][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:43])[CH3:41])=[O:38])[CH2:36]4)=[CH:29][CH:28]=3)[N:17]=2)[CH2:6][CH2:7]1)=[O:4]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 86712288tert-Butyl 3-(4-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 86712289tert-Butyl 3-(4-((4-(2-(1-(methoxycarbonyl)cyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylateYield 99.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 10% Pd/C (200 mg), tert-butyl 3-(4-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate (A7) (353 mg, 0.596 mmol) and Et3N (1.5 mL) in DMF (10 mL) was stirred with under a hydrogen atmosphere for 16 hours. The resulting mixture was diluted with EtOAc (60 mL), filtered through Celite and the volatiles were removed under reduced pressure. The residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to give the title compound A8 as yellow oil (353 mg, 99%); 1H NMR (400 MHz, d6-DMSO) δ 10.22 (s, 1H), 8.69 (s, 1H), 7.74 (d, J=8.6 Hz, 2H), 7.32-7.26 (m, 5H), 7.22-7.16 (m, 1H), 4.24 (t, J=7.4 Hz, 2H), 3.87-3.71 (m, 3H), 3.49 (s, 3H), 3.17-2.98 (m, 4H), 1.58 (d, J=3.3 Hz, 2H), 1.40 (s, 9H), 1.19 (s, 2H). LCMS-A: rt 6.650 min; m/z 595 [M−H]−.

Workup

  1. filtrationfiltered through Celite
  2. customthe volatiles were removed under reduced pressure
  3. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-a47bbec520574c6c85312f6002b86014
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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