Triethylamine → (R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide

HRID 1042644Notes

Reaction equation

HRID 1042644 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]([NH2:9])=[N:7][CH:8]=1)#[CH:2].[Si:10]([O:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:25]=2[NH:34][C:35](=[O:44])[C:36]2[CH:41]=[C:40](I)[CH:39]=[CH:38][C:37]=2[F:43])[CH2:19]1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].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>[NH2:9][C:6]1[N:7]=[CH:8][C:3]([C:1]#[C:2][C:40]2[CH:39]=[CH:38][C:37]([F:43])=[C:36]([CH:41]=2)[C:35]([NH:34][C:25]2[CH:26]=[C:27]([C:30]([F:31])([F:32])[F:33])[CH:28]=[CH:29][C:24]=2[N:20]2[CH2:21][CH2:22][CH2:23][C@@H:18]([O:17][Si:10]([C:13]([CH3:14])([CH3:15])[CH3:16])([CH3:11])[CH3:12])[CH2:19]2)=[O:44])=[CH:4][N:5]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 161090215-Ethynylpyrimidin-2-amineHCID 68463440(R)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluoro-5-iodobenzamide

Product 1

HCID 68459566(R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

In a 16×120 mm resealable pyrex tube, 5-ethynylpyrimidin-2-amine (0.080 g, 0.67 mmol), (R)—N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluoro-5-iodobenzamide (0.210 g, 0.34 mmol), Bis(triphenylphosphine)palladium(II) dichloride (0.012 g, 0.017 mmol), and Copper(I) iodide (0.0032 g, 0.017 mmol) were taken up in CH3CN and Triethylamine (0.71 ml, 5.1 mmol) was added, and the tube was flushed with nitrogen. The tube was sealed and the reaction heated to 70° C. overnight. The reaction was cooled, and transferred to a 50 mL RBF with EtOAc. The mixture was concentrated in vacuo, and the resulting solid was treated with 10% MeOH in CH2Cl2 and adsorbed onto 1.5 g silica gel and passed through a Redi-Sep® pre-packed silica gel column (40 g) eluting with 0-60% EtOAc/hexane. The product-containing fractions were concentrated to afford (R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(tert-butyldimethylsilyloxy)piperidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide as an off-white solid.

Workup

  1. customthe tube was flushed with nitrogen
  2. customThe tube was sealed
  3. temperatureThe reaction was cooled
  4. concentrationThe mixture was concentrated in vacuo
  5. additionthe resulting solid was treated with 10% MeOH in CH2Cl2
  6. washeluting with 0-60% EtOAc/hexane
  7. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-c94d6040c4c04190a38b574074ebb1b7
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Reaction notes

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