Cesium carbonate → HCID 57509990, compound

HRID 624155Notes

Reaction equation

HRID 624155 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([N:18]3[CH2:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:19]3)=[O:17])=[CH:11][CH:10]=2)O1.Cl[C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](=[O:39])[NH:31][N:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:39]=[C:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:29]([C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([N:18]3[CH2:19][C:20]4[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:26]3)=[O:17])=[CH:13][CH:14]=2)=[N:30][NH:31]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27751424-chlorophthalazin-1(2H)-oneHCID 68754457HCID 68754457, compound

Product 1

HCID 57509990HCID 57509990, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

105 mg N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)isoindoline-2-carboxamide (0.288 mmol) and 53 mg 4-chloro-1,2-dihydrophthalazin-1-one (0.288 mmol) were dissolved in 2.5 ml dioxane. Cesium carbonate (474 mg, 1.44 mmol) was dissolved in 0.25 ml water and the resulting solution added to the reaction mixture. After the addition of 27.8 mg [1,1′-bis(diphenylphosphino)-ferrocene]dichlorpalladium(II) (0.038 mmol) the reaction mixture was flushed with nitrogen and stirred for 30 minutes in the microwave (Biotage Initiator 2.5) at 110° C. Dioxane was removed under reduced pressure, water and dichloromethane added to the residue and the formed precipitation was filtered. After dissolving the solid matter in a larger amount of dichloromethane/methanol 8:2, silica gel was added and subsequently the solvent was removed under reduced pressure. This residue was was purified by column chromatography using dichloromethane/methanol 95:5. 1H NMR (DMSO-d6, 400 MHz): 6 ppm 12.73 (s, 1H), 8.55 (s, 1H), 8.33 (dd, 1H), 7.85-7.92 (m, 2H), 7.73-7.78 (m, 3H), 7.48 (d, 2H), 7.35-7.38 (m, 2H), 7.30-7.33 (m, 2H), 4.81 (s, 4H). MS (ESI(−)) m/e 383.2 (M+H)+.

Workup

  1. additionthe resulting solution added to the reaction mixture
  2. customwas flushed with nitrogen
  3. customDioxane was removed under reduced pressure, water and dichloromethane
  4. additionadded to the residue
  5. customthe formed precipitation
  6. filtrationwas filtered
  7. dissolutionAfter dissolving the solid matter in a larger amount of dichloromethane/methanol 8:2, silica gel
  8. additionwas added
  9. customsubsequently the solvent was removed under reduced pressure
  10. customThis residue was was purified by column chromatography

Sources & evidence

ORD record
ord-a003cbd2afd243068fe6ab2a80e2c285
Source dataset
uspto-grants-2016_04
Patent number
US09302989B2

Reaction notes

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