2,6-Lutidine → HCID 131730094, compound

HRID 2191069Notes

Reaction equation

HRID 2191069 reaction equation
[C:1]([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH:19]1[O:23][CH:22]([CH:24]=[CH:25][P:26]([O:30]C)([O:28]C)=[O:27])[CH:21]([O:32]C(=O)C2C=CC=CC=2)[CH:20]1[F:41])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:42]1C(C)=CC=CC=1C.C[Si](Br)(C)C.C(N(CC)CC)C>CC#N.CO>[NH4+:9].[NH4+:42].[C:1]([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[CH:19]1[O:23][CH:22]([CH:24]=[CH:25][P:26](=[O:27])([O-:28])[O-:30])[CH:21]([OH:32])[CH:20]1[F:41])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 8471TriethylamineHCID 76113BromotrimethylsilaneHCID 72247384HCID 72247384, compound

Product 1

HCID 131730094HCID 131730094, compoundYield 67.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

Compound 55.5 (92 mg, 0.16 mmol) in CH3CN (3.0 mL) was treated with 2,6-lutidine (183 μL, 1.6 mmol) and TMSBr (102 μL, 0.79 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 (446 μL, 3.2 mmol) in MeOH (2 mL). The mixture was warmed to r.t. and concentrated in vacuo. The residue was dissolved in concentrated NH4OH (1.5 mL) and warmed to 60° C. The solution was stirred for 2 h and then concentrated in vacuo. The residue was subjected to reverse phase HPLC eluting with 5-50% CH3CN-water gradient to give 55.6 (26 mg, 48% yield): white solid (bis-ammonium salt); 1H NMR (D2O, 300 MHz) 8.01 (s, 1H), 7.96 (s, 1H), 6.24 (m, 2H), 6.01 (app t, J=16 Hz, 1H), 5.23 (d, J=52.2 Hz, 1H), 4.44 (m, 2H), 4.31 (m, 1H); 31P NMR (D2O 121.4 MHz) 7.7; 19F NMR (D2O, 282 MHz) −203 (m, 1F); MS (ESI) m/z 345 [M+H]+.

Workup

  1. temperatureThe mixture was cooled to −40° C.
  2. temperatureThe mixture was warmed to r.t.
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in concentrated NH4OH (1.5 mL)
  5. temperaturewarmed to 60° C
  6. stirringThe solution was stirred for 2 h
  7. concentrationconcentrated in vacuo
  8. washHPLC eluting with 5-50% CH3CN-water gradient

Sources & evidence

ORD record
ord-8dab2a25b9cd4f7e96d9802205507980
Source dataset
uspto-grants-2012_12
Patent number
US08324179B2

Reaction notes

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