Triphenylphosphine → 4-Methylsulphanyl-7-(3-morpholinopropoxy)quinazoline

HRID 1597240Notes

Reaction equation

HRID 1597240 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([S:12][CH3:13])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[CH3:13][S:12][C:6]1[C:5]2[C:10](=[CH:11][C:2]([O:1][CH2:34][CH2:35][CH2:36][N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:3][CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 1995763-Morpholino-1-propanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1356740197-Hydroxy4-methylsulphanylquinazoline

Product 1

HCID 226492294-Methylsulphanyl-7-(3-morpholinopropoxy)quinazolineYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-Hydroxy-4-methylsulphanylquinazoline (2.5 g, 13 mmol) was suspended in methylene chloride (65 ml), triphenylphosphine (4.45 g, 17 mmol) was added followed by 4-(3-hydroxypropyl)morpholine (2.47 g, 17 mmol), (Bull Soc. Chim. Fr. 1962, 1117), and diethyl azodicarboxylate (2.92 g, 17 mmol) dropwise. After stirring for 1 hour the volatiles were removed by evaporation and the residue was partitioned between ethyl acetate/ether (20 ml/20 ml) and 1M hydrogen chloride (20 ml). The aqueous layer was separated and adjusted to pH9 with solid sodium hydrogen carbonate. The aqueous layer was extracted with methylene chloride. The organic layer was separated, washed with water, brine and dried (MgSO4). The volatiles were removed by evaporation and the residue was purified by chromatography eluting with methylene chloride/ethyl acetate/methanol (6/3/1 followed by 5/3/2 and 75/0/25) to give 4-methylsulphanyl-7-(3-morpholinopropoxy)quinazoline (2.03 g 49%).

Workup

  1. customwere removed by evaporation
  2. customthe residue was partitioned between ethyl acetate/ether (20 ml/20 ml) and 1M hydrogen chloride (20 ml)
  3. customThe aqueous layer was separated
  4. extractionThe aqueous layer was extracted with methylene chloride
  5. customThe organic layer was separated
  6. washwashed with water, brine
  7. dry with materialdried (MgSO4)
  8. customThe volatiles were removed by evaporation
  9. customthe residue was purified by chromatography
  10. washeluting with methylene chloride/ethyl acetate/methanol (6/3/1 followed by 5/3/2 and 75/0/25)

Sources & evidence

ORD record
ord-3c2517bd335f4efe8734f1fc30ed2adf
Source dataset
uspto-grants-2001_09
Patent number
US06294532B1

Reaction notes

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