Triethylamine → (8R,9R)-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

HRID 584842Notes

Reaction equation

HRID 584842 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:13]3[NH:12][C@H:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C@@H:10]([OH:20])[C:9](=[O:21])[C:8]=3[CH:7]=[CH:6][N:5]2[C:22]=1[CH3:23].C(N(CC)CC)C.[C:31](Cl)(=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33]>ClCCl>[CH3:1][C:2]1[N:3]=[C:4]2[C:13]3[NH:12][C@H:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[C@@H:10]([O:20][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[C:9](=[O:21])[C:8]=3[CH:7]=[CH:6][N:5]2[C:22]=1[CH3:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 59943673(8R,9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

Product 1

HCID 69552046(8R,9R)-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

140 g of (8R,9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one (WO 00/17200, example B1) are suspended in 1100 ml of dichloromethane under argon and with exclusion of moisture. After addition of 70 ml of triethylamine and 2.5 g of 4-dimethyl-aminopyridine, a solution of 62 ml of pivaloyl chloride in 70 ml of dichloromethane is added dropwise such that the temperature of the reaction mixture does not rise above 30° C. (cooling with a water bath). After stirring overnight, the mixture is added to 1 l of ice water and stirred in the cold for a further 10 min. The organic phase is separated off and the aqueous phase is extracted with dichloromethane (2×200 ml). The combined organic phases are washed with water (3×300 ml) until neutral, dried over sodium sulfate and evaporated. 220 g of yellowish oil are obtained, which is crystallized using 600 ml of tert-butyl methyl ether. After stirring in the cold for 2 h, the solid is filtered off, washed with 200 ml of tert-butyl methyl ether and the filter residue is dried to constant weight in a vacuum drying oven. 175 g (97%) of the title compound are obtained as a slightly yellowish solid of m.p. 185-187° C.

Workup

  1. customdoes not rise above 30° C.
  2. temperature(cooling with a water bath)
  3. stirringstirred in the cold for a further 10 min
  4. customThe organic phase is separated off
  5. extractionthe aqueous phase is extracted with dichloromethane (2×200 ml)
  6. washThe combined organic phases are washed with water (3×300 ml) until neutral,
  7. dry with materialdried over sodium sulfate
  8. customevaporated

Sources & evidence

ORD record
ord-63b78396931f4885bf5491d39dcb940c
Source dataset
uspto-grants-2005_08
Patent number
US06927292B2

Reaction notes

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