N,N-Dimethylaniline → HCID 68156097, compound

HRID 1877795Notes

Reaction equation

HRID 1877795 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=O)[C:9]3=[CH:13][C:14]([CH3:16])=[CH:15][N:8]3[CH2:7][C:6]=2[CH:17]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:29])=O>COC1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([Cl:29])[C:9]3=[CH:13][C:14]([CH3:16])=[CH:15][N:8]3[CH2:7][C:6]=2[CH:17]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychloride2×HCID 68155891HCID 68155891, compound

Product 1

HCID 68156097HCID 68156097, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 7-chloro-2-methyl-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (40.6 g, 164.58 mmoles) in methoxybenzene (250 mL) at 70° C. add N,N-dimethylaniline (2.8 equiv; 58.59 mL, 460.8 mmoles) in one portion followed by phosphoryl chloride (2.3 equiv (molar); 35.18 mL, 378.52 mmoles) over 20 minutes, controlling the exotherm by addition. Heat the resultant dark solution at 90° C. for 1.5 h. Add additional phosphoryl chloride (0.33 equiv; 5.05 mL, 54.31 mmoles) and heat the mixture at 90° C. for a further 1 h to give complete conversion. Evaporate to near dryness and partition the residue between water (500 mL) and ethyl acetate (2×500 mL). Combine organic layers and wash with water (500 mL) then brine. Dry over Na2SO4, filter and evaporate onto silica. Pass through a silica gel pad with iso-hexane/ethyl acetate (gradient elution 5 to 25%). Combine product fractions and evaporate to a small amount of solvent. Add iso-hexane (150 mL) and collect the resulting yellow powder by filtration, to give 7,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine (34.0 g, 78% yield). MS (m/z): 265.1 (M+1).

Workup

  1. additionby addition
  2. temperatureheat the mixture at 90° C. for a further 1 h
  3. customto give complete conversion
  4. customEvaporate
  5. custompartition the residue between water (500 mL) and ethyl acetate (2×500 mL)
  6. washCombine organic layers and wash with water (500 mL)
  7. dry with materialDry over Na2SO4
  8. filtrationfilter
  9. customevaporate onto silica
  10. customCombine product fractions and evaporate to a small amount of solvent
  11. customAdd iso-hexane (150 mL) and collect the resulting yellow powder
  12. filtrationby filtration

Sources & evidence

ORD record
ord-4e19ac6465354196b8ca8ab4f55b197b
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

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