Triethylamine → 2-chloro-8-chloromethyl-5,11-dihydro-11-ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

HRID 724966Notes

Reaction equation

HRID 724966 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]3[CH:18]=[C:17]([CH2:19]O)[CH:16]=[N:15][C:9]=3[N:10]([CH2:13][CH3:14])[C:11]=2[N:12]=1.S(Cl)([Cl:25])=O.C(N(CC)CC)C.[OH-].[Na+]>C(Cl)(Cl)Cl.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]3[CH:18]=[C:17]([CH2:19][Cl:25])[CH:16]=[N:15][C:9]=3[N:10]([CH2:13][CH3:14])[C:11]=2[N:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 10615550HCID 10615550, compound

Product 1

HCID 108307382-chloro-8-chloromethyl-5,11-dihydro-11-ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-oneYield 94.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

The 2-chloro-5,11-dihydro-11-ethyl-8-hydroxymethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (0.52 g, 1.6 mmol) was dissolved in chloroform (10 mL) and treated with thionyl chloride (0.12 mL, 1.6 mmol) followed by triethylamine (0.23 mL, 1.6 mmol). After 0.5 hours stirring the mixture was made alkaline with 15% aqueous sodium hydroxide, diluted with brine (10 mL) and the organic layer was separated. The aqueous layer was then extracted with dichloromethane (2×20 mL). The combined organics were dried over sodium sulfate, filtered, concentrated and the residue was purified by flash chromatography (gradient hexanes to 1:1 hexanes/ethyl acetate) to give the title compound (0.51 g, 93%), m.p. 133°-134° C.

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was then extracted with dichloromethane (2×20 mL)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by flash chromatography (gradient hexanes to 1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-74783ae67d934ed89557648205037a90
Source dataset
uspto-grants-1998_01
Patent number
US05705499

Reaction notes

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