Dimethylacetamide → HCID 118116230, compound

HRID 1754841Notes

Reaction equation

HRID 1754841 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]=[CH:15][S:16][C:10]=2[CH:9]1[C:17]1[CH:22]=[C:21](Br)[CH:20]=[CH:19][C:18]=1[O:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:31][N:32](C)C(=O)C>CCOC(C)=O.O.[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]=[CH:15][S:16][C:10]=2[CH:9]1[C:17]1[CH:22]=[C:21]([C:31]#[N:32])[CH:20]=[CH:19][C:18]=1[O:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 31374DimethylacetamideHCID 90022175HCID 90022175, compound

Product 1

HCID 118116230HCID 118116230, compound

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (±)-4-(5-bromo-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester (375 mg, 0.75 mmol, 1.00 eq.) in N,N-dimethylacetamide (1.5 mL), zinc cyanide (44 mg, 0.37 mmol, 0.50 eq.), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 16 μmol, 0.02 eq.), 1,1′-bis-(diphenylphosphino)-ferrocene (11 mg, 20 μmol, 0.03 eq.) and poly(methylhydrosiloxane) (15 μL) were added in sequence. The resulting mixture was stirred at 150° C. under microwave irradiation for 30 min. To the previous mixture, zinc cyanide (44 mg, 0.37 mmol, 0.50 eq.), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 16 μmol, 0.02 eq.), 1,1′-bis-(diphenylphosphino)-ferrocene (11 mg, 20 μmol, 0.03 eq.) and poly(methylhydrosiloxane) (15 μL) were added. The resulting mixture was stirred at 150° C. under microwave irradiation for 30 min. The reaction mixture was diluted with AcOEt and water was added. The layers were separated and the org. layer was dried over MgSO4, filtered over celite, and concentrated in vacuo. The residue, redissolved in DMF (4 mL) and formic acid (0.2 mL), was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated to give the title compound as a brown oil.

Workup

  1. stirringThe resulting mixture was stirred at 150° C. under microwave irradiation for 30 min
  2. additionwas added
  3. customThe layers were separated
  4. dry with materiallayer was dried over MgSO4
  5. filtrationfiltered over celite
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue, redissolved in DMF (4 mL)
  8. customformic acid (0.2 mL), was purified by prep
  9. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated

Sources & evidence

ORD record
ord-70210a96871f422c99363509fc1901fd
Source dataset
uspto-grants-2015_10
Patent number
US09169270B2

Reaction notes

Loading…