N,N-Dimethylaniline → 2-(4-Chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

HRID 657729

Reaction equation

HRID 657729 reaction equation
CO[C:3]1[C:4]2[CH2:12][N:11]([C:13]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:14]=3[C:15]#[N:16])[CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1.CN(C)C1C=CC=CC=1.CN(C)C=O.P(Cl)(Cl)([Cl:38])=O.[OH-].[Na+]>C(#N)C>[Cl:38][C:3]1[C:4]2[CH2:12][N:11]([C:13]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:14]=3[C:15]#[N:16])[CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 5

HCID 949N,N-DimethylanilineHCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychloride2×HCID 598407122-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

Product 1

HCID 598406882-(4-Chloro-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-methylbenzonitrile (4.15 g, 14.1 mmol), N,N-dimethylaniline (0.181 mL, 1.4 mmol), N,N-dimethylformamide (0.21 mL, 2.7 mmol) and acetonitrile (35 mL) was heated to dissolve at 105° C. Phosphoryl chloride (5.3 mL, 56 mmol) was added dropwise over 3 mins, and the reaction was heated to reflux at 110° C. After 40 mins, additional phosphoryl chloride (5.3 mL, 0.056 mol) was added dropwise over 3 mins. After another 20 hours, 1H NMR showed that the reaction was ca 70% complete and the reaction mixture was allowed to cool and poured over ice (200 g) and 45% aq. NaOH (75 mL) was added. The mixture was extracted with CH2Cl2 (3×200 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by silica gel column (0-100% EtOAc/hexane) to yield a brown oil which became a solid in the freezer.

Workup

  1. temperaturewas heated
  2. dissolutionto dissolve at 105° C
  3. temperaturethe reaction was heated
  4. waitAfter another 20 hours
  5. temperatureto cool
  6. additionwas added
  7. extractionThe mixture was extracted with CH2Cl2 (3×200 mL)
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column (0-100% EtOAc/hexane)
  11. customto yield a brown oil which

Sources & evidence

ORD record
ord-eb2ee39ba4c8484b87eab6fb412d03ab
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Linked notes

Loading…