Triphenylphosphine → HCID 68905447, compound

HRID 546503Notes

Reaction equation

HRID 546503 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].Br[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17]([NH:19][C@@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C@@H:21]1[NH:26][C:27]([C:29]1[S:30][C:31]3[CH2:32][N:33]([CH3:38])[CH2:34][CH2:35][C:36]=3[N:37]=1)=[O:28])=[O:18])=[CH:11]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])O.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl.O1CCCC1.CN(C)C=O.C(N(CC)CC)C>[CH3:38][N:33]1[CH2:34][CH2:35][C:36]2[N:37]=[C:29]([C:27]([NH:26][C@@H:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C@@H:20]3[NH:19][C:17]([C:12]3[NH:13][C:14]4[C:10]([CH:11]=3)=[CH:9][C:8]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])=[CH:16][CH:15]=4)=[O:18])=[O:28])[S:30][C:31]=2[CH2:32]1

Participants

10

Reactant 4

HCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 516892Sodium BicarbonateHCID 67188711HCID 67188711, compound

Product 1

HCID 68905447HCID 68905447, compound

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

Triethylamine (6 ml), N,N-dimethylformamide (5 ml), trimethylsilylacetylene (0.250 ml) and palladium acetate (20 mg) were added to a tetrahydrofuran solution (2 ml) of (±)-cis-N1-[(5-bromoindol-2-yl)carbonyl]-N2-[(5 methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine (300 mg) and triphenylphosphine (70 mg) at room temperature. After stirring at 90° C. for 2 hours, the reaction mixture was allowed to cool to room temperature, and dichloromethane (20 ml) and a saturated aqueous solution (30 ml) of sodium hydrogencarbonate were added to conduct liquid separation. The resultant water layer was extracted with dichloromethane (3×10 ml), the organic layers were collected and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain residue. The resultant residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:acetone:methanol=10:10:1) to obtain a mixture mainly containing (±)-cis-N1-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-N2-[[5-(trimethylsilylethynyl)indol-2-yl]carbonyl]-1,2-cyclohexanediamine as a colorless solid. This product was dissolved in methanol (6 ml), potassium carbonate (120 mg) was added, and the mixture was stirred for 1 hour. Dichloromethane (20 ml) and water (20 ml) were added to the reaction mixture to conduct liquid separation. The resultant water layer was extracted with dichloromethane (2×15 ml), the organic layers were collected and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:acetone:methanol=10:10:1) and dissolved in water-methanol-dichloromethane. The resultant solution was then concentrated to obtain the title compound (72 mg) as a pale yellow solid.

Workup

  1. temperatureto cool to room temperature
  2. customliquid separation
  3. extractionThe resultant water layer was extracted with dichloromethane (3×10 ml)
  4. customthe organic layers were collected
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customto obtain residue
  8. customThe resultant residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:acetone:methanol=10:10:1)

Sources & evidence

ORD record
ord-dcc024e80a6c4d519388a090e24400f6
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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