Sodium hydride → N,N-dibenzyl-3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine

HRID 1969852Notes

Reaction equation

HRID 1969852 reaction equation
[H-].[Na+].[CH2:3]([N:10]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:11]1[CH2:15][CH:14]([CH3:16])[CH:13]([C:17]2[N:21]3[C:22]4[CH:28]=[CH:27][NH:26][C:23]=4[N:24]=[CH:25][C:20]3=[N:19][CH:18]=2)[CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:36][Si:37]([CH2:40][CH2:41][O:42][CH2:43]Cl)([CH3:39])[CH3:38]>CN(C=O)C>[CH2:29]([N:10]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH:11]1[CH2:12][CH:13]([C:17]2[N:21]3[C:22]4[CH:28]=[CH:27][N:26]([CH2:43][O:42][CH2:41][CH2:40][Si:37]([CH3:39])([CH3:38])[CH3:36])[C:23]=4[N:24]=[CH:25][C:20]3=[N:19][CH:18]=2)[CH:14]([CH3:16])[CH2:15]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58557511N,N-dibenzyl-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentanamine

Product 1

HCID 58557169N,N-dibenzyl-3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamineYield 60.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To the suspension of sodium hydride (60% dispersion in mineral oil, 0.382 g, 9.55 mmol) in DMF (50 mL) was added a solution of N,N-dibenzyl-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentanamine (3.96 g, 9.09 mmol) in DMF (50 mL) drop-wise at about 0° C. The resulting solution was stirred at ambient temperature for about 10 min. SEM chloride (1.774 mL, 10.0 mmol) was added drop-wise and the solution was stirred for about 1 h. The solvent was removed under reduced pressure and the residue was partitioned between water and EtOAc (200 mL each). The organic layer was washed with brine (100 mL), dried over anhydrous MgSO4, filtered and concd. The residue was purified by silica gel column chromatography eluting with 10-80% EtOAc in DCM to yield N,N-dibenzyl-3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine (3.1 g, 60% yield) as an off-white amorphous solid. LC/MS (Table 1, Method a) Rt=3.32 min; MS m/z 566 (M+H)+.

Workup

  1. stirringthe solution was stirred for about 1 h
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between water and EtOAc (200 mL each)
  4. washThe organic layer was washed with brine (100 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with 10-80% EtOAc in DCM

Sources & evidence

ORD record
ord-87d3e42df6884bc091ea802b669a6601
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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