Sodium hydride → HCID 67338630, compound

HRID 1045107Notes

Reaction equation

HRID 1045107 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:8])[CH2:6][OH:7].Cl[C:10]1[C:11]([C:31]2[CH:36]=[CH:35][C:34]([C:37]3[NH:38][N:39]=[CH:40][CH:41]=3)=[CH:33][CH:32]=2)=[CH:12][C:13]2[N:17]=[C:16](S(C)(=O)=O)[N:15]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]=2[CH:30]=1>C1COCC1.C(#N)C>[N:39]1[NH:38][C:37]([C:34]2[CH:35]=[CH:36][C:31]([C:11]3[CH:10]=[CH:30][C:14]4[N:15]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:27])([CH3:28])[CH3:29])[C:16]([O:7][CH2:6][C:5]([OH:4])=[O:8])=[N:17][C:13]=4[CH:12]=3)=[CH:32][CH:33]=2)=[CH:41][CH:40]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 66774Methyl GlycolateHCID 58387138HCID 58387138, compound2×

Product 1

HCID 67338630HCID 67338630, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 20 mL scintillation vial equipped with a septum cap and a magnetic stirring bar was charged under N2 with NaH (18.0 mg, 60% suspension in mineral oil, 0.45 mmol). A solution of hydroxyacetic acid methyl ester (81.0 mg, 0.90 mmol) in THF (1.5 mL) was added dropwise to the vial. Immediately after the addition was complete, a solution of 6-chloro-2-methanesulfonyl-5-[4-(2H-pyrazol-3-yl)-phenyl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazole (compound 45-1, 75.0 mg, 0.150 mmol) in THF (1 mL) was added. The resulting suspension was stirred at rt for 5 min, then diluted with ACN (2 mL) and quenched by slow addition of water (2 mL). The resulting solution was stirred at rt for 5 min, and then additional 15 min at 65° C. The solution was acidified with 5% aqueous HCl and extracted with EtOAc (three times, 3 mL). The organic layers were combined and washed with 5% aqueous HCl and water and evaporated to dryness in vacuo to give the title compound as yellowish oil. LR-MS (API-ES): mixture of two N-SEM isomers, calculated for C24H27ClN4O4Si 498.2, observed m/e 499.0 (M+H)+ (Rt 3.01, 3.15 min). The compound was used in the next step without further purification.

Workup

  1. customA 20 mL scintillation vial equipped with a septum
  2. customcap
  3. additionImmediately after the addition
  4. customquenched by slow addition of water (2 mL)
  5. stirringThe resulting solution was stirred at rt for 5 min
  6. customadditional 15 min
  7. customat 65° C
  8. extractionextracted with EtOAc (three times, 3 mL)
  9. washwashed with 5% aqueous HCl and water
  10. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-6974b4b5d11f44efb5d1c9b35fca5cf2
Source dataset
uspto-grants-2013_10
Patent number
US08563746B2

Reaction notes

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