Triethylamine → (S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

HRID 502695Notes

Reaction equation

HRID 502695 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][C:33](I)=[CH:32][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=1[N:17]1[CH2:22][CH2:21][CH2:20][C@H:19]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:18]1)=[O:5].[C:37]([C:39]1[CH:40]=[N:41][C:42]([NH2:45])=[N:43][CH:44]=1)#[CH:38].C(N(CC)CC)C>CC#N.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.[Cu]I>[NH2:45][C:42]1[N:43]=[CH:44][C:39]([C:37]#[C:38][C:33]2[CH:34]=[CH:35][C:2]([F:1])=[C:3]([CH:32]=2)[C:4]([NH:6][C:7]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:8]=2[N:17]2[CH2:22][CH2:21][CH2:20][C@H:19]([N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:18]2)=[O:5])=[CH:40][N:41]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 161090215-Ethynylpyrimidin-2-amineHCID 16109029(S)-tert-butyl 1-(2-(2-fluoro-5-iodobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

Product 1

HCID 16109030(S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

In a 25-mL RBF (S)-tert-butyl 1-(2-(2-fluoro-5-iodobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate (0.496 g, 0.80 mmol), 5-ethynylpyrimidin-2-amine (0.19 g, 1.6 mmol), Bis(triphenylphosphine)palladium(II) dichloride (0.028 g, 0.040 mmol), and Copper(I) iodide (0.0076 g, 0.040 mmol) were taken up in CH3CN and Triethylamine (1.7 ml, 12 mmol) was added, and the tube was flushed with nitrogen. The tube was sealed and the reaction heated to 70 deg. C. for 16 h. The reaction was cooled and transfered to a larger flask with EtOAc and concentrated in vacuo. The solid was adsorbed onto 4 g silica gel from 10% MeOH/MC purified by Isco {Redi-Sep® pre-packed silica gel column (80 g); eluent 0-75% EtOAc/hexanes over 30 min}. Product-containing fractions were concentrated to afford (S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate as a orange foam. MS m/z=613 [M+H]+. Calc'd for C31H32F4N6O3: 612.

Workup

  1. customthe tube was flushed with nitrogen
  2. customThe tube was sealed
  3. temperaturethe reaction heated to 70 deg. C
  4. temperatureThe reaction was cooled
  5. customtransfered to a larger flask with EtOAc
  6. concentrationconcentrated in vacuo
  7. custompurified by Isco {Redi-Sep® pre-packed silica gel column (80 g)
  8. waiteluent 0-75% EtOAc/hexanes over 30 min}
  9. concentrationProduct-containing fractions were concentrated

Sources & evidence

ORD record
ord-80f2562f39bd47c986d1ce78deee946b
Source dataset
uspto-grants-2010_08
Patent number
US07776869B2

Reaction notes

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