Ammonia → (7R,8R,9R)-10-Acetyl-7-hydroxy-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 584844Notes

Reaction equation

HRID 584844 reaction equation
[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16]([CH3:17])[N:11]3[CH:10]=[CH:9][C:8]=2[C:7](=[O:19])[C@H:6]([O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C@H:5]1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)(=[O:3])[CH3:2].C([BH3-])#N.[Na+].Cl.N>C(O)(C)C.CN(C1C=CC(N=NC2C=CC(S(O)(=O)=O)=CC=2)=CC=1)C.ClCCl>[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16]([CH3:17])[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([OH:19])[C@H:6]([O:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C@H:5]1[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 69551548(8R,9R)-10-Acetyl-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h]-[1,7]naphthyridin-7-one

Product 1

HCID 69263320(7R,8R,9R)-10-Acetyl-7-hydroxy-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridineYield 96.5%

Reagents, catalysts & solvents 3

HCID 11037Benzenesulfonic acid, 4-(2-(4-(dimethylamino)phenyl)diazenyl)-CatalystHCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
16 °C

Procedure

165 g of (8R,9R)-10-acetyl-2,3-dimethyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h]-[1,7]naphthyridin-7-one are suspended in 2.0 l of isopropanol with mechanical stirring. 47.8 g of sodium cyanoborohydride are then introduced with ice cooling. After addition of 20 drops of Methyl Orange, methanolic hydrogen chloride solution is slowly added dropwise until the color change to red persists (approximately 150 ml, 1 h, warming of the reaction mixture to 16° C.). After a further 20 min, the mixture is added to 1.5 l of ice water and 1 l of dichloromethane and neutralized with ammonia solution (25%). The organic phase is separated off and the aqueous phase is extracted with 250 ml of dichloromethane. The combined organic phases are reextracted with water (3×1.5 l), dried over sodium sulfate and evaporated on a rotary evaporator. Coevaporation with acetone (3×) and drying of the residue in a high vacuum yields 160 g (90%) of the title compound as a colorless foam of m.p. 103-105° C., which is used without further purification in the next stage.

Workup

  1. additionis slowly added dropwise until the color change to red persists (approximately 150 ml, 1 h
  2. customThe organic phase is separated off
  3. extractionthe aqueous phase is extracted with 250 ml of dichloromethane
  4. dry with materialdried over sodium sulfate
  5. customevaporated on a rotary evaporator
  6. dry with materialCoevaporation with acetone (3×) and drying of the residue in a high vacuum

Sources & evidence

ORD record
ord-8f379e092ef641a991655ec73e85ed13
Source dataset
uspto-grants-2005_08
Patent number
US06927292B2

Reaction notes

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