Methanesulfonic Acid → (7S,8R,9R)-8-hydroxy-2-methyl-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 985086Notes

Reaction equation

HRID 985086 reaction equation
[OH:1][C@@H:2]1[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@H:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@H:3]1[OH:22].CS(O)(=O)=O.[CH3:28][O:29][CH2:30][CH2:31]O>>[OH:22][C@H:3]1[C@@H:2]([O:1][CH2:31][CH2:30][O:29][CH3:28])[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH:22][C@H:3]1[C@H:2]([O:1][CH2:31][CH2:30][O:29][CH3:28])[C:11]2[CH:10]=[CH:9][N:8]3[CH:12]=[C:13]([CH3:15])[N:14]=[C:7]3[C:6]=2[NH:5][C@@H:4]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 80192-MethoxyethanolHCID 10125504(7R,8R,9R)-7,8-Dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

Product 2

HCID 9968444(7S,8R,9R)-8-hydroxy-2-methyl-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridineYield 23%HCID 10286852(7R,8R,9R)-8-hydroxy-2-methyl-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridineYield 13%

Conditions

Temperature
65 °C

Procedure

6 g (20.3 mmol) of (7R,8R,9R)-7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridine are introduced into 75 ml of ethylene glycol monomethyl ether at 65° C., treated with 4.9 g (50.8 mmol) of methanesulfonic acid and the mixture is stirred at 65° C. for 1.5 h. The reaction solution is concentrated in a rotary evaporator and residue is treated with 50 ml of dichloromethane and 50 ml of water. The aqueous phase is adjusted to pH 8 by means of saturated sodium hydrogencarbonate solution, the organic phase is separated oft and the aqueous phase is extracted twice using 20 ml of dichloromethane each time. The combined dichloromethane phases are concentrated and the residue is separated by chromatography on silica gel (ethyl acetate/2-propanol/conc. ammonia water 98:2:0.1). The individual product fractions are concentrated and the products are dried at 50° C. in a high vacuum. 1.7 g (23% of theory) of (7S,8R,9R)-8-hydroxy-2-methyl-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine (12a) of m.p. 149-152° C. and 0.9 g (13% of theory) of (7R,8R,9R)-8-hydroxy-2-methyl-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridine (12b) of m.p. 108-110° C. are obtained.

Workup

  1. concentrationThe reaction solution is concentrated in a rotary evaporator and residue
  2. additionis treated with 50 ml of dichloromethane and 50 ml of water
  3. customthe organic phase is separated oft
  4. extractionthe aqueous phase is extracted twice
  5. concentrationThe combined dichloromethane phases are concentrated
  6. customthe residue is separated by chromatography on silica gel (ethyl acetate/2-propanol/conc. ammonia water 98:2:0.1)
  7. concentrationThe individual product fractions are concentrated
  8. customthe products are dried at 50° C. in a high vacuum

Sources & evidence

ORD record
ord-005a9bb5f2fb4d899234cf721ce2f7c9
Source dataset
uspto-grants-2005_03
Patent number
US06869949B2

Reaction notes

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