Hydrochloric Acid → HCID 57791823, compound

HRID 1091779Notes

Reaction equation

HRID 1091779 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]([N:23]2[CH2:28][CH2:27][CH:26]([O:29][CH3:30])[CH2:25][CH2:24]2)=[O:22])[CH:15]=1.C1(C(C2C=CC=CC=2)=[NH:38])C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Cl>C(O[Pd]OC(=O)C)(=O)C.O1CCOCC1>[NH2:38][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][N:6]=[C:5]2[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([C:21]([N:23]2[CH2:28][CH2:27][CH:26]([O:29][CH3:30])[CH2:25][CH2:24]2)=[O:22])[CH:15]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57791842HCID 57791842, compound

Product 1

HCID 57791823HCID 57791823, compoundYield 13.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

6-bromo-4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1 (2H)-one (98) (0.2 g, 0.42 mmol), diphenylmethanimine (0.076 g, 0.42 mmol) and cesium carbonate (0.275 g, 0.84 mmol) were added to dioxane (15 mL) and the system was degassed using nitrogen. To this was added diacetoxypalladium (0.019 g, 0.08 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.073 g, 0.13 mmol), the reaction was heated at 95° C. for 2 hours. The reaction mixture was quenched with water (50 mL), extracted with EtOAc (3×50 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford brown gum. This was stirred with 2.0N HCl (5.0 mL) for 1 hour, the reaction mixture was quenched with 2M NaOH (10 mL), extracted with EtOAc (3×15 mL), the organic layer was dried over MgSO4, filtered and evaporated to afford brown gum. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (0.024 g, 13.87%); 1H NMR (500.133 MHz, DMSO) δ 1.47-1.38 (2H, m), 1.82-1.73 (2H, m), 2.89 (3H, s), 3.23-3.16 (2H, m), 3.27 (2H, s), 3.46-3.41 (1H, m), 4.13 (2H, s), 5.78 (2H, s), 6.87 (1H, d), 7.00 (1H, dd), 7.14 (1H, t), 7.22 (1H, dd), 7.38-7.34 (1H, m), 7.93 (1H, d), 11.60 (1H, s); m/z (LC-MS, ESI+), RT=1.56 (M+H 411).

Workup

  1. customthe system was degassed
  2. customThe reaction mixture was quenched with water (50 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford brown gum
  8. customthe reaction mixture was quenched with 2M NaOH (10 mL)
  9. extractionextracted with EtOAc (3×15 mL)
  10. dry with materialthe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. customevaporated
  13. customto afford brown gum
  14. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  15. additionFractions containing the desired compound
  16. customwere evaporated to dryness

Sources & evidence

ORD record
ord-067d24810f7a4f708c9b638a757e05ca
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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