Sodium hydride → HCID 69586206, compound

HRID 723410Notes

Reaction equation

HRID 723410 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-a49e4d8def8c48ec836354761d6372bb
Source dataset
uspto-grants-2006_11
Patent number
US07141567B2

Reaction notes

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