Potassium Carbonate → 3-(1-(5-oxa-2-aza-bicyclo[2.2.1]heptan-2-yl)phthalazin-6-yl)-N-cyclopropyl-4-methylbenzamide

HRID 2357577Notes

Reaction equation

HRID 2357577 reaction equation
Cl.[CH:2]12[CH2:8][CH:5]([NH:6][CH2:7]1)[CH2:4][O:3]2.C(=O)([O-])[O-].Br[C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[C:20](Cl)=[N:19][N:18]=[CH:17]2.C(=O)([O-])[O-].[K+].[K+].[CH:31]1([NH:34][C:35](=[O:52])[C:36]2[CH:41]=[CH:40][C:39]([CH3:42])=[C:38](B3OC(C)(C)C(C)(C)O3)[CH:37]=2)[CH2:33][CH2:32]1>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.COCCOC.CCO.C(#N)C>[CH:5]12[CH2:8][CH:2]([O:3][CH2:4]1)[CH2:7][N:6]2[C:20]1[C:21]2[C:16](=[CH:15][C:14]([C:38]3[CH:37]=[C:36]([CH:41]=[CH:40][C:39]=3[CH3:42])[C:35]([NH:34][CH:31]3[CH2:32][CH2:33]3)=[O:52])=[CH:23][CH:22]=2)[CH:17]=[N:18][N:19]=1

Participants

11

Reactant 5

HCID 11430Potassium CarbonateHCID 19660Carbonate IonHCID 219143642-Oxa-5-azabicyclo[2.2.1]heptane hydrochlorideHCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 220304246-Bromo-1-chlorophthalazine

Product 1

HCID 684556113-(1-(5-oxa-2-aza-bicyclo[2.2.1]heptan-2-yl)phthalazin-6-yl)-N-cyclopropyl-4-methylbenzamideYield 127.6%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of 2-oxa-5-aza-bicyclo[2.2.1]heptane hydrochloride (223 mg, 1643 μmol) in 10 mL methanol was treated with MP-carbonate (1 g, 3.2 mmol) at 22° C. for 1 h. The mixture was filtered and concentrated. The residue, 6-bromo-1-chlorophthalazine (Example 1, 100 mg, 411 μmol), potassium carbonate (57 mg, 411 μmol) and 5 mL acetonitrile was added to a glass microwave reaction vessel. The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 190° C. for 20 min. The mixture was concentrated under vacuum and N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (124 mg, 411 μmol), tetrakis(triphenylphosphine)palladium (475 mg, 411 μmol), 5 mL DME/EtOH (4:1) and 0.6 mL H2O were added. The mixture was stirred at 90° C. for 1 h., then directly transferred to silica gel and purified via flash chromatography (silica gel) eluting with a gradient of 2% 2 M ammonia in MeOH/DCM to 10% 2 M ammonia in MeOH/DCM to give the title compound (0.21g) as a yellow solid. Found MS (ES+): 401 (M+H)+.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. additionwere added
  4. stirringThe mixture was stirred at 90° C. for 1 h.
  5. custompurified via flash chromatography (silica gel)
  6. washeluting with a gradient of 2% 2 M ammonia in MeOH/DCM to 10% 2 M ammonia in MeOH/DCM

Sources & evidence

ORD record
ord-3506393d89ec412680257ed956653a83
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

Loading…