2,6-Lutidine → HCID 131730094, compound

HRID 2191070Notes

Reaction equation

HRID 2191070 reaction equation
C[O:2][P:3]([CH:7]=[CH:8][CH:9]1[CH:13]([O:14][Si](CC)(CC)CC)[CH:12]([F:22])[CH:11]([N:23]2[CH:31]=[N:30][C:29]3[C:24]2=[N:25][CH:26]=[N:27][C:28]=3[NH:32][C:33](=[O:40])[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:10]1)(=[O:6])[O:4]C.[N:41]1C(C)=CC=CC=1C.C[Si](Br)(C)C.C(N(CC)CC)C.[F-].[NH4+]>CC#N.CO.CN(C=O)C>[NH4+:23].[NH4+:41].[C:33]([NH:32][C:28]1[N:27]=[CH:26][N:25]=[C:24]2[C:29]=1[N:30]=[CH:31][N:23]2[CH:11]1[O:10][CH:9]([CH:8]=[CH:7][P:3](=[O:2])([O-:4])[O-:6])[CH:13]([OH:14])[CH:12]1[F:22])(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

9

Reactant 5

HCID 79372,6-LutidineHCID 8471TriethylamineHCID 25516Ammonium fluorideHCID 76113BromotrimethylsilaneHCID 86641137HCID 86641137, compound

Product 1

HCID 131730094HCID 131730094, compoundYield 55.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

Compound 56.2 (338 mg, 0.57 mmol) in CH3CN (6.0 mL) was treated with 2,6-lutidine (662 μL, 5.7 mmol) and TMSBr (368 μL, 2.9 mmol) at 0° C. for 30 min. The mixture was warmed to r.t. and stirred for 30 min. The mixture was cooled to −40° C. and treated with triethylamine (794 μL, 5.7 mmol) in MeOH (2 mL). The mixture was warmed to r.t. and concentrated in vacuo. The residue in DMF (2.0 mL) was treated with ammonium fluoride (1.06 g, 28.5 mmol) and heated to 80° C. for 5 h. The solvent was removed in vacuo and residue was subjected to reverse phase HPLC eluting with 5-50% CH3CN-water gradient to give 56.3 (76 mg, 30% yield, 2 steps): white solid; 1H NMR (CD3OD, 300 MHz) 8.71 (s, 1H), 8.49 (s, 1H), 6.75 (d, J=8.1 Hz, 2H), 7.61 (app t, J=6.6 Hz, 1H), 7.52 (m, 2H), 6.71 (m, 2H), 6.15 (t, J=18.3 Hz, 1H), 5.17 (d, J=52.5 Hz, 1H), 4.50 (m, 2H); 31P NMR (D2O 121.4 MHz) 12.2; 19F NMR (D2O, 282 MHz) −200 (m, 1F); MS (ESI) m/z 451 [M+H]+.

Workup

  1. temperatureThe mixture was cooled to −40° C.
  2. temperatureThe mixture was warmed to r.t.
  3. concentrationconcentrated in vacuo
  4. temperatureheated to 80° C. for 5 h
  5. customThe solvent was removed in vacuo and residue
  6. washHPLC eluting with 5-50% CH3CN-water gradient

Sources & evidence

ORD record
ord-5664f47491b74a1dbd01a6eb5290a223
Source dataset
uspto-grants-2012_12
Patent number
US08324179B2

Reaction notes

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