N,N,N',N'-Tetramethylethylenediamine → HCID 86690206, compound

HRID 868807Notes

Reaction equation

HRID 868807 reaction equation
[CH3:1][C:2]1[S:6][C:5]2[NH:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[C:4]=2[CH:3]=1.CN(C)CCN(C)C.[Li]CCCC.Cl[C:37]([O:39][CH2:40][Cl:41])=[O:38]>O1CCCC1>[CH3:1][C:2]1[S:6][C:5]2[N:7]([C:37]([O:39][CH2:40][Cl:41])=[O:38])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[N:14]=[C:15]([N:16]3[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 62754Chloromethyl chloroformateHCID 135398745OlanzapineHCID 178418339Butyllithium

Product 1

HCID 86690206HCID 86690206, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of olanzapine (5.0 g, 16 mmol) in tetrahydrofuran (50 mL) at −78° C. was added tetramethylethylenediamine (2.4 mL, 16 mmol), followed by 2M n-BuLi in hexanes (8.0 mL, 16 mmol) over 5 min. The reaction mixture was stirred for 15 min and then chloromethyl chloroformate (2.1 mL, 24 mmol) added and the reaction mixture stirred a further 30 min. The reaction mixture was then warmed to room temperature, stirred for 1 h and quenched with water (50 mL). This mixture was diluted with brine (50 mL) and extracted with ethyl acetate (50 mL). The organic phase was dried over MgSO4, evaporated and the residue further purified by column chromatography on silica eluting with 0.2:1:1 methanol/dichloromethane/ethyl acetate to give chloromethyl 2-methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine-10-carboxylate [C] (5.6 g, ˜50% pure by 1H NMR and LCMS). This was used directly in the next reaction without further purification.

Workup

  1. stirringthe reaction mixture stirred a further 30 min
  2. stirringstirred for 1 h
  3. customquenched with water (50 mL)
  4. additionThis mixture was diluted with brine (50 mL)
  5. extractionextracted with ethyl acetate (50 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. customevaporated
  8. customthe residue further purified by column chromatography on silica eluting with 0.2:1:1 methanol/dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-855fe6ea138748f8b7ef3738cb46c918
Source dataset
uspto-grants-2015_03
Patent number
US08969337B2

Reaction notes

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