Hydrochloric Acid → 11-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

HRID 2426485Notes

Reaction equation

HRID 2426485 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-:29].[Mg+2].C[O-].Br[CH2:34][CH2:35][CH2:36][CH2:37]Cl.Cl>CO.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:37][CH2:36][CH2:35][CH2:34][O:17][C:16](=[O:29])[C:12]3=2)[C:7]1=[O:23]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 813641-Bromo-4-chlorobutaneHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497, compound

Product 1

HCID 5934472111-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.80 g, 2.19 mmol; Example 1, step 9) and magnesium methoxide in methanol (10.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (22 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The residual DMSO solution was treated with 1-bromo-4-chlorobutane (1.80 g, 10.50 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The reaction mixture was heated at 100° C. for 3 hrs. The reaction mixture was treated with dilute HCl. The solid precipitated was filtered, dissolved in DMSO, and subjected to reverse phase HPLC purification. Collection and lyophilzation of appropriate fractions provided the title compound.

Workup

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. temperatureThe reaction mixture was heated at 100° C. for 3 hrs
  3. customThe solid precipitated
  4. filtrationwas filtered
  5. dissolutiondissolved in DMSO
  6. customphase HPLC purification
  7. customCollection and lyophilzation of appropriate fractions

Sources & evidence

ORD record
ord-69ceaf36d5714d669080c3c6ad323546
Source dataset
uspto-grants-2011_06
Patent number
US07968564B2

Reaction notes

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