Phosphorus oxychloride → 7-(Benzyloxy)-4-chloro-6-methoxyquinoline

HRID 1686045Notes

Reaction equation

HRID 1686045 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:13]1[C:12]2[C:17](=[CH:18][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[C:10]([O:20][CH3:21])[CH:11]=2)[N:16]=[CH:15][CH:14]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178486758HCID 178486758, compound

Product 1

HCID 226465627-(Benzyloxy)-4-chloro-6-methoxyquinoline

Procedure

7-Benzyloxy-6-methoxy-quinolin-4-ol (WO2006108059) (1 g) was refluxed with POCl3 (8 ml) for 3 hours. The reaction was evaporated and dissolved into DCM (80 ml) that was washed with ice water followed by brine. The organic layer was dried with Na2SO4 and evaporated to dryness to give a dark yellow solid as 4-chloro-7-benzyloxy-6-methoxy-quinoline that was mixed with 5-aminoindole (600 mg) in isopropanol (15 ml). The mixture was refluxed for one hour and cooled to RT and the precipitate was filtered to give the product as 4-(1H-indol-5-ylamino)-7-benzyloxy-6-methoxy-quinoline (710 mg). This product was mixed with Pd/C (10%, 100 mg) in EtOH (80 ml) and hydrogenated at 50 psi for 8 hours to give a gray suspension that was evaporated to dryness as 4-(1H-indol-5-ylamino)-7-hydroxy-6-methoxy-quinoline (˜85% purity) for next step without further purification.

Workup

  1. customThe reaction was evaporated
  2. dissolutiondissolved into DCM (80 ml) that
  3. washwas washed with ice water
  4. dry with materialThe organic layer was dried with Na2SO4
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-cb58778db44f41b6b4603e665b617afd
Source dataset
uspto-grants-2012_04
Patent number
US08148532B2

Reaction notes

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