Trimethyl borate → HCID 58557409, compound

HRID 1969547Notes

Reaction equation

HRID 1969547 reaction equation
[C:1](=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.COB(OC)OC.[CH2:33]([C@H:35]1[C@@H:39]([C:40]2[N:44]3[C:45]4[C:51](I)=[CH:50][N:49]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[C:46]=4[N:47]=[CH:48][C:43]3=[N:42][N:41]=2)[CH2:38][C@@H:37]([N:61]([CH2:68][O:69][CH2:70][CH2:71][Si:72]([CH3:75])([CH3:74])[CH3:73])[S:62]([CH:65]2[CH2:67][CH2:66]2)(=[O:64])=[O:63])[CH2:36]1)[CH3:34]>O1CCOCC1.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]>[CH2:33]([C@H:35]1[C@@H:39]([C:40]2[N:44]3[C:45]4[C:51]([CH3:1])=[CH:50][N:49]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[C:46]=4[N:47]=[CH:48][C:43]3=[N:42][N:41]=2)[CH2:38][C@@H:37]([N:61]([CH2:68][O:69][CH2:70][CH2:71][Si:72]([CH3:75])([CH3:74])[CH3:73])[S:62]([CH:65]2[CH2:67][CH2:66]2)(=[O:64])=[O:63])[CH2:36]1)[CH3:34]

Participants

7

Reactant 4

HCID 8470Trimethyl borateHCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 67998641HCID 67998641, compound

Product 1

HCID 58557409HCID 58557409, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Cesium carbonate (0.274 g, 0.841 mmol), tricyclohexylphosphine (20 wt % solution in toluene, 0.094 g, 0.067 mmol), Pd2(dba)3 (0.039 g, 0.042 mmol) and trimethylborate (0.069 g, 0.547 mmol) were added to a solution of N-((1S,3R,4S)-3-ethyl-4-(8-iodo-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)-N-((2-(trimethylsilyl)ethoxy)methyl)cyclopropanesulfonamide (0.32 g, 0.421 mmol, prepared using KK from Preparation #GGG.1) in 1,4-dioxane (8 mL). The mixture was degassed and heated at about 85° C. for about 2 h. The solvent was removed and the residue was partitioned between EtOAc and water (20 mL each). The organic phase was washed with brine (15 mL), dried over anhydrous MgSO4, filtered and concd. The resulting mixture was purified by silica gel flash chromatography (40 to 100% of EtOAc in heptane) to yield N-((1S,3R,4S)-3-ethyl-4-(8-methyl-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)-N-((2-(trimethylsilyl)ethoxy)methyl)cyclopropanesulfonamide (0.21 g, 77%) as a yellow amorphous solid. LC/MS (Table 1, Method a) Rt=3.39 min; MS m/z: 650 (M+H)+.

Workup

  1. customThe mixture was degassed
  2. customThe solvent was removed
  3. customthe residue was partitioned between EtOAc and water (20 mL each)
  4. washThe organic phase was washed with brine (15 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe resulting mixture was purified by silica gel flash chromatography (40 to 100% of EtOAc in heptane)

Sources & evidence

ORD record
ord-f80968f5f9724a22bc626e9ce916e8bf
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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