Sodium hydride → HCID 69586206, compound

HRID 985109Notes

Reaction equation

HRID 985109 reaction equation
[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:17])=[CH:16][N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([OH:18])[C@H:6]([O:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:5]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:3])[CH3:2].O([CH2:40][CH2:41][O:42][CH3:43])S(C(F)(F)F)(=O)=O.[H-].[Na+]>ClCCl.CN1CCCC1=O>[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:17])=[CH:16][N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:18][CH2:40][CH2:41][O:42][CH3:43])[C@H:6]([O:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:5]1[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 222734932-Methoxyethyl trifluoromethanesulfonateHCID 69586755HCID 69586755, compound

Product 1

HCID 69586206HCID 69586206, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a of −30° C. cooled solution of 7.40 g (17.6 mmol) (7R,8R,9R)-10-acetyl-7-hydroxy-2-methyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine in dichloromethane (25 ml) and N-methyl-pyrrolidinone (25 ml) is added 4.00 g (19.3 mmol) methoxyethyl triflate and 1.40 g (35.2 mmol) sodium hydride and it is stirred for further 2 h at this temperature. The reaction is quenched by adding of saturated aqueous ammonium chloride solution. Subsequently the mixture is extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulphate and evaporated in vacuo. The crude product is purified by column chromatography (ethyl acetate/cyclohexane/triethylamine: 5/4/1) to give 7.50 g (15.63 mmol/89%) of the title compound as a yellow amorphous solid. 1H-NMR (200 MHz,[D6] DMSO): δ=1.19 (s, 9H), 2.15 (s, 3H), 2.38 (s, 3H), 3.27 (s, 3H), 3.45-3.57 (m, 2H), 3.83-3.93 (m, 2H), 4.60 (d, 1H), 5.31 (t, 1H), 5.79 (d, 1H), 6.94 (s, 1H), 7,20 (s, 5H), 7.74 (s, 1H), 8.43 (d, 1H).

Workup

  1. customThe reaction is quenched
  2. additionby adding of saturated aqueous ammonium chloride solution
  3. extractionSubsequently the mixture is extracted twice with dichloromethane
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over sodium sulphate
  6. customevaporated in vacuo
  7. customThe crude product is purified by column chromatography (ethyl acetate/cyclohexane/triethylamine: 5/4/1)

Sources & evidence

ORD record
ord-51269a2b3007440cb5ec25b52c76a818
Source dataset
uspto-grants-2005_03
Patent number
US06869949B2

Reaction notes

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