Dichloromethane → HCID 178466069, compound

HRID 711415Notes

Reaction equation

HRID 711415 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][C:5]=1[F:13])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl.I[C:24]1[N:28]2[C@@H:29]([CH2:34][C:35]3[N:36]=[CH:37][N:38](S(N(C)C)(=O)=O)[CH:39]=3)[CH2:30][NH:31][C:32](=[O:33])[C:27]2=[CH:26][C:25]=1[C:46]1[CH:51]=[CH:50][CH:49]=[C:48]([O:52][C:53]([F:56])([F:55])[F:54])[CH:47]=1>O1CCOCC1.O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:24]2[N:28]3[C@@H:29]([CH2:34][C:35]4[N:36]=[CH:37][NH:38][CH:39]=4)[CH2:30][NH:31][C:32](=[O:33])[C:27]3=[CH:26][C:25]=2[C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([O:52][C:53]([F:54])([F:56])[F:55])[CH:47]=2)=[CH:6][C:5]=1[F:13])[CH3:2]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 2782821(4-Ethoxy-3-fluorophenyl)boronic acidHCID 867325644-({(4S)-6-iodo-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide

Product 1

HCID 178466069HCID 178466069, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

(4-ethoxy-3-fluorophenyl)boronic acid (0.072 g, 0.39 mmol), cesium carbonate (0.096 g, 0.3 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium (0.008 g, 0.010 mmol) complex with dichloromethane, were subsequently added to a degassed solution of 4-({(4S)-6-iodo-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (0.06 g, 0.1 mmol) in 3 ml of 1,4-dioxane and 1 ml of water, under argon. The mixture was heated at 100° for 3 hours in a sealed vial. The reaction was portioned between ethyl acetate and water, the organic layer dried over sodium sulphate and the solvent removed in vacuo. 4-({(4S)-6-(4-ethoxy-3-fluorophenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide was submitted to the next step without purification. The crude was dissolved in a mixture 1:1 of water (2 ml) and 4N HCl in dioxane (2 ml) and heated at 75° C. until deprotection was completed. After evaporation under vacuo, purification by RP-HPLC afforded the title compound as a white solid.

Workup

  1. temperatureThe mixture was heated at 100° for 3 hours in a sealed vial
  2. dry with materialthe organic layer dried over sodium sulphate
  3. customthe solvent removed in vacuo
  4. custom4-({(4S)-6-(4-ethoxy-3-fluorophenyl)-1-oxo-7-[3-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-4-yl}methyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide was submitted to the next step without purification
  5. dissolutionThe crude was dissolved in a mixture 1:1 of water (2 ml) and 4N HCl in dioxane (2 ml)
  6. customAfter evaporation
  7. customunder vacuo, purification by RP-HPLC

Sources & evidence

ORD record
ord-7ae1ac74f46a4c81bfb5c976df801189
Source dataset
uspto-grants-2015_11
Patent number
US09181258B2

Reaction notes

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