Sodium hydride → HCID 178455298, compound

HRID 81273Notes

Reaction equation

HRID 81273 reaction equation
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][OH:13])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[Cl:14][C:15]1[N:20]=[C:19]([C:21]2[C:22](F)=[N:23][CH:24]=[C:25]([Cl:27])[CH:26]=2)[C:18]2[N:29]([CH2:41][C@H:42]3[CH2:47][CH2:46][C@H:45]([CH3:48])[CH2:44][CH2:43]3)[C:30]([N:32]3[CH2:37][CH2:36][O:35][C@@H:34]4[CH2:38][CH2:39][CH2:40][C@@H:33]34)=[N:31][C:17]=2[CH:16]=1>CN(C=O)C>[Si:3]([O:10][CH2:11][CH2:12][O:13][C:22]1[C:21]([C:19]2[C:18]3[N:29]([CH2:41][C@H:42]4[CH2:47][CH2:46][C@H:45]([CH3:48])[CH2:44][CH2:43]4)[C:30]([N:32]4[CH2:37][CH2:36][O:35][C@@H:34]5[CH2:38][CH2:39][CH2:40][C@@H:33]45)=[N:31][C:17]=3[CH:16]=[C:15]([Cl:14])[N:20]=2)=[CH:26][C:25]([Cl:27])=[CH:24][N:23]=1)([C:6]([CH3:8])([CH3:9])[CH3:7])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111376652-(tert-Butyl(dimethyl)silyl)oxyethanolHCID 178461232HCID 178461232, compound

Product 1

HCID 178455298HCID 178455298, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (24 mg, 0.6 mmol) was added to solution of 2-((tert-butyldimethylsilyl)oxy)ethanol (70 mg, 0.4 mmol) in DMF (1.0 mL) at 0° C., and the reaction was stirred at 0° C. for 30 minutes. A solution of 6-chloro-4-(5-chloro-2-fluoropyridin-3-yl)-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic, Example 18.1, Step 1; 100 mg, 0.2 mmol) was added, and the reaction was stirred at 0° C. for 30 minutes. The reaction was quenched by adding saturated aqueous NH4Cl solution and extracted using EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. Purification of the residue on a silica gel column with 0 to 50% EtOAc/hexane afforded 4-[2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)-5-chloropyridin-3-yl]-6-chloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic). MS APCl calc'd. for C34H49Cl2N5O3Si [M+H]+ 674. found 674.

Workup

  1. stirringthe reaction was stirred at 0° C. for 30 minutes
  2. customThe reaction was quenched
  3. additionby adding saturated aqueous NH4Cl solution
  4. extractionextracted
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the residue on a silica gel column with 0 to 50% EtOAc/hexane

Sources & evidence

ORD record
ord-26ff98dd5d0a4e1b9259da8cf017ed63
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

Loading…