Sarcosine → 2-Bromo-6-{4,4-dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}-4-fluorobenzaldehyde

HRID 519409Notes

Reaction equation

HRID 519409 reaction equation
[CH3:1][C:2]1([CH3:15])[CH2:13][C:12]2[S:11][C:10]3[C:9](=[O:14])[NH:8][N:7]=[CH:6][C:5]=3[C:4]=2[CH2:3]1.[Br:16][C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21](Br)[C:18]=1[CH:19]=[O:20].N(CC(O)=O)C.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[Br:16][C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([N:8]2[N:7]=[CH:6][C:5]3[C:4]4[CH2:3][C:2]([CH3:15])([CH3:1])[CH2:13][C:12]=4[S:11][C:10]=3[C:9]2=[O:14])[C:18]=1[CH:19]=[O:20]

Participants

6

Reactant 4

HCID 1088SarcosineHCID 11430Potassium CarbonateHCID 444746662,6-Dibromo-4-fluorobenzaldehydeHCID 866837837,7-Dimethyl-7,8-dihydro-3H-cyclopenta[4,5]thieno[2,3-d]pyridazin-4(6H)-one

Product 1

HCID 866837822-Bromo-6-{4,4-dimethyl-9-oxo-7-thia-10,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),11-trien-10-yl}-4-fluorobenzaldehyde

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A 100-mL round bottom flask equipped with a magnetic stirrer and a reflux condenser was charged with 131h (330 mg, 1.5 mmol), 2,6-dibromo-4-fluorobenzaldehyde (1.26 g, 4.5 mmol), CuBr (113 mg, 0.8 mmol), sarcosine (142 mg, 1.6 mmol), K2CO3 (420 mg, 3.0 mmol), and dioxane (20 mL). See FIG. 15. After three cycles of vacuum/argon flush, the mixture was heated at 95° C. for 15 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography 5:1 eluting with petroleum ether/ethyl acetate to 131i as a white solid (380 mg, 60%). MS-ESI: [M+H]+ 420.6

Workup

  1. customA 100-mL round bottom flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica-gel column chromatography 5:1 eluting with petroleum ether/ethyl acetate to 131i as a white solid (380 mg, 60%)

Sources & evidence

ORD record
ord-30d387d301b142e48f3435e8a3291e9e
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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