4-(3-Chloropropyl)morpholine → HCID 11755761, compound

HRID 973588Notes

Reaction equation

HRID 973588 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:19]=[C:18]([N:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH3:21])[C:17]2[C:12](=[C:13]([OH:28])[CH:14]=[CH:15][CH:16]=2)[N:11]=1.[Na].[O:30]1[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38]Cl)[CH2:32][CH2:31]1>C(O)C.C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:19]=[C:18]([N:20]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH3:21])[C:17]2[C:12](=[C:13]([O:28][CH2:38][CH2:37][CH2:36][N:33]3[CH2:34][CH2:35][O:30][CH2:31][CH2:32]3)[CH:14]=[CH:15][CH:16]=2)[N:11]=1

Participants

6

Reactant 3

HCID 958344-(3-Chloropropyl)morpholineHCID 5360545SodiumHCID 10044934HCID 10044934, compound

Product 1

HCID 11755761HCID 11755761, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 1140TolueneSolvent

Procedure

2-(2-Methyl-4-fluorophenylamino)-4-(N-methylphenylamino)-8-hydroxyquinazoline (1.6 g, 4.3 mmol) was suspended in ethanol (25 ml) and to the stirred suspension was added a solution of sodium (0.1 g, 4.3 mmol) in ethanol (15 ml). Stirring was continued for 15 minutes and the mixture evaporated to dryness. The residue was dissolved in toluene (50 ml) and heated to reflux temperature. To this refluxing solution was added a freshly prepared solution of 3-morpholinopropyl chloride base (from 1.28 g, 6.4 mmol of hydrychloride salt) in toluene (20 ml). Refluxing was continued overnight and after cooling the mixture was washed with sodium carbonate solution and water, dried and evaporared. The residual oil was chromatographed on silica gel using CH2Cl2 as eluting solvent. After evaporation of the relevent fractions the residue was crystallised from diethyl ether/pentane to give the title compound (1.5 g, 71%) m.p. 133°-134°.

Workup

  1. customthe mixture evaporated to dryness
  2. dissolutionThe residue was dissolved in toluene (50 ml)
  3. temperatureheated
  4. temperatureto reflux temperature
  5. temperatureRefluxing
  6. waitwas continued overnight
  7. temperatureafter cooling the mixture
  8. washwas washed with sodium carbonate solution and water
  9. customdried
  10. customThe residual oil was chromatographed on silica gel
  11. washas eluting solvent
  12. customAfter evaporation of the relevent fractions the residue
  13. customwas crystallised from diethyl ether/pentane

Sources & evidence

ORD record
ord-2c1166ab8a4d49c4b6f74c57fc867656
Source dataset
uspto-grants-1991_11
Patent number
US05064833

Reaction notes

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