Tetrahydrofuran → HCID 66818620, compound

HRID 1755013Notes

Reaction equation

HRID 1755013 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH2:9][CH2:10][S:11]([N:14]2[CH2:31][CH2:30][C:17]3([N:21]=[C:20]([CH:22]4[CH2:27][CH2:26][CH:25]([CH3:28])[CH2:24][CH2:23]4)[NH:19][C:18]3=[O:29])[CH2:16][CH2:15]2)(=[O:13])=[O:12])=[C:4]([CH3:32])[C:3]=1I.[C:34]([N:38]=[C:39]=[O:40])([CH3:37])([CH3:36])[CH3:35].C(N(CC)C(C)C)(C)C.[C]=O.[O:52]1CCC[CH2:53]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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:34]([N:38]1[C:53](=[O:52])[C:3]2[C:2](=[CH:7][C:6]([CH3:8])=[C:5]([CH2:9][CH2:10][S:11]([N:14]3[CH2:31][CH2:30][C:17]4([N:21]=[C:20]([CH:22]5[CH2:27][CH2:26][CH:25]([CH3:28])[CH2:24][CH2:23]5)[NH:19][C:18]4=[O:29])[CH2:16][CH2:15]3)(=[O:13])=[O:12])[C:4]=2[CH3:32])[NH:1][C:39]1=[O:40])([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 62412tert-Butyl isocyanate2×HCID 81531Diisopropylethylamine2×HCID 86672777HCID 86672777, compoundHCID 178418416HCID 178418416, compound2×

Product 1

HCID 66818620HCID 66818620, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×

Procedure

A mixture of 8-[2-(4-amino-3-iodo-2,6-dimethyl-phenyl)-ethanesulfonyl]-2-(4-methyl-cyclohexyl)-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (15 mg, 0.0256 mmol), palladium acetate (1.1 mg, 5.11 μmol), 1,1′-bis(diphenylphosphino)ferrocene (2.2 mg, 5.11 μmol), tert-butyl isocyanate (12 μL, 0.0767 mmol) and N,N-diisopropylethylamine (13 μL, 0.0767 mmol) in tetrahydrofuran (1 mL) was heated with stirring for 12 hours in a pressure bottle sealed under the conditions of 4 atm and 80° C. in a carbon monoxide atmosphere. After returning to room temperature, palladium acetate (2.2 mg, 10.22 μmol), 1,1′-bis(diphenylphosphino)ferrocene (4.4 mg, 10.22 μmol), tert-butyl isocyanate (24 μL, 0.153 mmol) and N,N-diisopropylethylamine (26 μL, 0.153 mmol) were added to the reaction solution, and the mixture was heated with stirring for 14 hours in a pressure bottle sealed under the conditions of 4 atm and 80° C. in a carbon monoxide atmosphere. After returning to room temperature, the reaction solution was concentrated under reduced pressure, and the resulting residue was purified by preparative TLC to give 3-tert-butyl-5,7-dimethyl-6-{2-[2-(4-methyl-cyclohexyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl]-ethyl}-1H-quinazoline-2,4-dione as a pale yellow solid (3.3 mg, 22%).

Workup

  1. temperaturewas heated
  2. customAfter returning to room temperature
  3. temperaturethe mixture was heated
  4. stirringwith stirring for 14 hours in a pressure bottle
  5. customAfter returning to room temperature
  6. concentrationthe reaction solution was concentrated under reduced pressure
  7. customthe resulting residue was purified by preparative TLC

Sources & evidence

ORD record
ord-dd729cda116b4956a2a91f097cd60533
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

Loading…