Trimethylsilyldiazomethane → HCID 178505452, compound

HRID 2105526Notes

Reaction equation

HRID 2105526 reaction equation
[Si]([CH:5]=[N+:6]=[N-:7])(C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[CH:16][C:17]2[N:21]=[C:20]([CH:22]3[CH2:27][CH2:26][N:25]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([C:35]5[C:42]([C:43]6[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=6)=[CH:41][C:38]([C:39]#[N:40])=[CH:37][N:36]=5)=[CH:31][CH:30]=4)[CH2:24][CH2:23]3)[NH:19][C:18]=2[CH:49]=1>C1COCC1>[F:13][C:14]1[CH:15]=[CH:16][C:17]2[N:21]=[C:20]([CH:22]3[CH2:27][CH2:26][N:25]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([C:35]5[C:42]([C:43]6[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=6)=[CH:41][C:38]([C:39]6[N:40]=[N:7][NH:6][CH:5]=6)=[CH:37][N:36]=5)=[CH:31][CH:30]=4)[CH2:24][CH2:23]3)[NH:19][C:18]=2[CH:49]=1

Participants

5

Reactant 3

HCID 167693TrimethylsilyldiazomethaneHCID 11431759HCID 11431759, compoundHCID 178418339Butyllithium

Product 1

HCID 178505452HCID 178505452, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of TMS diazomethane (2 M in hexanes, 0.205 mL, 0.410 mmol) in anhydrous THF (1 mL) was added n-butyl lithium (2.5 M in hexanes, 0.164 mL, 0.410 mmol) dropwise@−5° C. The mixture was stirred to 20 min@−5° C. when this solution was added dropwise to a mixture of 6-(4-{[4-(6-fluoro-1H-benzimidazol-2-yl)piperidin-1-yl]methyl}phenyl)-5-phenylnicotinonitrile (4-1, 0.050 g, 0.103 mmol) in THF (1 mL)@−5° C. The reaction was allowed to stir@−5° C. for 3 hr when it was quenched with saturated aqueous Na2HCO3 and extracted with CH2Cl2 (3×15 mL). The combined organics were dried (anhydrous Na2SO4), filtered, and concentrated. The residue was taken up in THF (2 mL) and TBAF (1 M in THF, 0.205 mL) was added. The reaction was heated to 60° C. for 2 hr, at which time it was cooled and concentrated. The resulting residue was taken up in DMF and purified by reverse phase HPLC (8-1; 5% CH3CN: 95% H2O+0.01% TFA to 95% CH3CN: 5% H2O+0.01% TFA). 1H-NMR (500 MHz, d6 DMSO) δ 9.74 (bs, 1H), 9.20 (d, J=2.20, 1H), 8.65 (bs, 1H), 8.29 (d, J=2.21, 1H), 7.60-7.70 (m, 1H), 7.25-7.55 (m, 12H), 7.18 (t, J=7.08, 1H), 4.35 (s, 2H), 3.50 (d, J=12.06, 2H), 3.25-3.39 (m, 1H), 3.09-3.20 (m, 2H), 2.29-2.39 (m, 2H), 1.97-2.10 (m, 2H). HRMS m/z (M+H) Calcd: 530.2463, found: 530.2454.

Workup

  1. stirringto stir@−5° C. for 3 hr when it
  2. customwas quenched with saturated aqueous Na2HCO3
  3. extractionextracted with CH2Cl2 (3×15 mL)
  4. dry with materialThe combined organics were dried (anhydrous Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionTBAF (1 M in THF, 0.205 mL) was added
  8. temperatureThe reaction was heated to 60° C. for 2 hr, at which time it
  9. temperaturewas cooled
  10. concentrationconcentrated
  11. custompurified by reverse phase HPLC (8-1; 5% CH3CN: 95% H2O+0.01% TFA to 95% CH3CN: 5% H2O+0.01% TFA)

Sources & evidence

ORD record
ord-51dd251e6ac7484993ab324135e5eac8
Source dataset
uspto-grants-2009_08
Patent number
US07579355B2

Reaction notes

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