Toluene → 8-(1,1-Dioxidothiomorpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]-phthalazin-1(2H)-one

HRID 920922Notes

Reaction equation

HRID 920922 reaction equation
Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH2:13][CH2:14][C:15]1[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=1)[N:8]=[CH:7]2.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1.[NH:38]1[CH2:43][CH2:42][S:41](=[O:45])(=[O:44])[CH2:40][CH2:39]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.O>[O:44]=[S:41]1(=[O:45])[CH2:42][CH2:43][N:38]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[C:10](=[O:12])[N:9]([CH2:13][CH2:14][C:15]2[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=2)[N:8]=[CH:7]3)[CH2:39][CH2:40]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 6484228Thiomorpholine 1,1-dioxideHCID 717436398-Chloro-2-(2-(quinolin-2-YL)ethyl)phthalazin-1(2H)-one

Product 1

HCID 866831348-(1,1-Dioxidothiomorpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]-phthalazin-1(2H)-oneYield 67.2%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave reaction vial was charged with the 8-chloro-2-(2-(quinolin-2-yl)ethyl)phthalazin-1(2H)-one from Example 98.4 (100 mg, 0.30 mmol), Cs2CO3 (194 mg, 0.59 mmol), Pd2(dba)3 (5.45 mg, 5.96 μmol) and BINAP (11.13 mg, 0.018 mmol). The solids were purged with argon for 1 h. A separate flask was charged with toluene (993 μl) and thiomorpholin 1,1-dioxide (48.3 mg, 0.36 mmol), degas with argon for 1 h and then transferred to the microwave reaction vial under inert conditions. The resulting reaction mixture was heated on microwave at 100° C. for 20 h. The reaction mixture was poured into water and extracted with DCM. The solids were removed. The organic layer was washed with water, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified on a silica column (eluent: DCM/methanol) and then recrystallized from EA to afford the title product (87 mg, 67.2%).

Workup

  1. customA microwave reaction
  2. customThe solids were purged with argon for 1 h
  3. customdegas with argon for 1 h
  4. customtransferred to the microwave reaction vial under inert conditions
  5. customThe resulting reaction mixture
  6. extractionextracted with DCM
  7. customThe solids were removed
  8. washThe organic layer was washed with water
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified on a silica column (eluent: DCM/methanol)
  13. customrecrystallized from EA

Sources & evidence

ORD record
ord-0fc32b55b3044b0a8028d6ad109a8048
Source dataset
uspto-grants-2016_03
Patent number
US09273068B2

Reaction notes

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