Thionyl Chloride → 9-benzyloxy-2-(3-chlorobenzyl)-7-(2,2-dimethylbutyryl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione

HRID 1349499Notes

Reaction equation

HRID 1349499 reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:31])[C:11]([C:28](O)=[O:29])=[CH:12][N:13]2[CH2:18][CH2:17][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:15](=[O:27])[C:14]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:36][C:37]([Mg]Cl)([CH3:40])[CH2:38][CH3:39].CCOCC.S([O-])(O)(=O)=O.[K+]>O1CCCC1.O.C(OCC)(=O)C.C(N(CC)CC)C>[CH2:1]([O:8][C:9]1[C:10](=[O:31])[C:11]([C:28](=[O:29])[C:37]([CH3:40])([CH3:36])[CH2:38][CH3:39])=[CH:12][N:13]2[CH2:18][CH2:17][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[C:15](=[O:27])[C:14]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 24386Thionyl ChlorideHCID 516920Potassium bisulfateHCID 230775239-benzyloxy-2-(3-chlorobenzyl)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acidHCID 178467772HCID 178467772, compound

Product 1

HCID 230774849-benzyloxy-2-(3-chlorobenzyl)-7-(2,2-dimethylbutyryl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

9-Benzyloxy-2-(3-chlorobenzyl)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid (200 mg) obtained in Example 219, Step 2 was suspended in tetrahydrofuran (6 ml), and triethylamine (0.07 ml) and thionyl chloride (0.037 ml) were added at room temperature with stirring. After stirring at room temperature for 10 min, the mixture was cooled to −78° C. and 1.0 M 1,1-dimethylpropylmagnesium chloride/ether solution was added dropwise. After further stirring at the same temperature for 20 min, 5% aqueous potassium hydrogen sulfate solution (5 ml) and ethyl acetate (6 ml) were added, and water (5 ml) was further added. The mixture was extracted twice with ethyl acetate-tetrahydrofuran (1:1, 30 ml each). The organic layer was dried and concentrated, and ethyl acetate was added to the residue. The obtained solid was collected by filtration to give 9-benzyloxy-2-(3-chlorobenzyl)-7-(2,2-dimethylbutyryl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,8-dione (59 mg).

Workup

  1. stirringAfter stirring at room temperature for 10 min
  2. stirringAfter further stirring at the same temperature for 20 min
  3. extractionThe mixture was extracted twice with ethyl acetate-tetrahydrofuran (1:1, 30 ml each)
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. additionethyl acetate was added to the residue
  7. filtrationThe obtained solid was collected by filtration

Sources & evidence

ORD record
ord-1c98debadbab4c33b5df6cb7d75d9def
Source dataset
uspto-grants-2007_05
Patent number
US07211572B2

Reaction notes

Loading…