Tetrahydrofuran → HCID 86612116, compound

HRID 2114827Notes

Reaction equation

HRID 2114827 reaction equation
[F:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]3[C:13]4[CH2:30][CH2:29][NH:28][C:27](=[O:31])[C:14]=4[C:15]([O:16][S:17]([C:20]4[C:21]([CH3:26])=[CH:22][CH:23]=[CH:24][CH:25]=4)(=[O:19])=[O:18])=[C:9]3[C:8]2=[O:32])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.Br[CH2:51][C:52]1[CH:57]=[CH:56][N:55]=[CH:54][CH:53]=1>CN(C=O)C.C(OCC)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]3[C:13]4[CH2:30][CH2:29][N:28]([CH2:51][C:52]5[CH:57]=[CH:56][N:55]=[CH:54][CH:53]=5)[C:27](=[O:31])[C:14]=4[C:15]([O:16][S:17]([C:20]4[C:21]([CH3:26])=[CH:22][CH:23]=[CH:24][CH:25]=4)(=[O:19])=[O:18])=[C:9]3[C:8]2=[O:32])=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 6427994-(Bromomethyl)pyridineHCID 2733832Lithium HexamethyldisilazideHCID 86612117HCID 86612117, compound

Product 1

HCID 86612116HCID 86612116, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a cold (0° C.) solution of 8-(4-fluorobenzyl)-10-toluenesulfonyloxy-3,4,7,8-tetrahydropyrido-[3′,4′:4,5]pyrrolo[1,2-a]pyrazine-1,9(2H,6H)-dione (60 mg, 0.12 mmol) in anhydrous DMF (1 mL), a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 1.5 eq) was added. The mixture was stirred at the same temperature for 30 minutes. A solution of 4-bromomethylpyridine in diethyl ether (generated from the corresponding hydrobromide salt through partition between aq sodium carbonate and ether, and drying the solution by passing it through a plug of activated basic alumina). The reaction mixture was stirred at rt for one hour and concentrated under vacuum. The residue was subjected to reverse phase preparative HPLC purification. Collection and lyophilization of appropriate fractions provided the titled compounds.

Workup

  1. customthrough partition between aq sodium carbonate and ether
  2. customdrying the solution
  3. stirringThe reaction mixture was stirred at rt for one hour
  4. concentrationconcentrated under vacuum
  5. customphase preparative HPLC purification
  6. customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record
ord-5fe0e5660e9e4dca90ed054d9aba34d5
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

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