Trimethylsilylacetylene → HCID 58635322, compound

HRID 1351608Notes

Reaction equation

HRID 1351608 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([C@@H:18]3[CH2:20][C@H:19]3[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:17])[CH2:12][CH2:11]2)=[N:6][CH:7]=1.[CH3:27][Si:28]([C:31]#[CH:32])([CH3:30])[CH3:29]>CS(C)=O.C(NCC)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[C:21]1([C@@H:19]2[CH2:20][C@H:18]2[C:16]([N:13]2[CH2:14][CH2:15][CH:10]([CH2:9][NH:8][C:5]3[N:4]=[CH:3][C:2]([C:32]#[C:31][Si:28]([CH3:30])([CH3:29])[CH3:27])=[CH:7][N:6]=3)[CH2:11][CH2:12]2)=[O:17])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 58635320HCID 58635320, compound

Product 1

HCID 58635322HCID 58635322, compound

Reagents, catalysts & solvents 5

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 8021DiethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-N-[(1-{[(1R,2R)-2-phenylcyclopropyl]carbonyl}piperidin-4-yl)methyl]pyrimidin-2-amine (EXAMPLE 153) (0.300 g, 0.722 mmol), trimethylsilylacetylene (0.177 g, 1.81 mmol), Pd(PPh3)4 (0.083 g, 0.072 mmol), and copper iodide (0.007 g, 0.036 mmol) in DMSO (1 mL) and diethylamine (1 mL) was heated in a sealed tube at 100° C. for 3 h. The reaction mixture was cooled to RT, diluted with ethyl acetate (50 mL), washed with water (10 mL), and brine (10 mL), then dried over Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel 60 (35 g), eluting with 10:1-10:89-80 CH2Cl2:2-propanol:hexane to give the title compound.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with water (10 mL), and brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel 60 (35 g)
  7. washeluting with 10:1-10:89-80 CH2Cl2

Sources & evidence

ORD record
ord-9252e1db2aea492ab9dc6982aefd0f7f
Source dataset
uspto-grants-2007_05
Patent number
US07217716B2

Reaction notes

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