Sodium Carbonate → HCID 118021500, compound

HRID 518572Notes

Reaction equation

HRID 518572 reaction equation
[CH3:1][N:2]1[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:21].[CH2:22]([C:24]1[O:25][C:26]2[C:32](I)=[CH:31][C:30]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:29][C:27]=2[CH:28]=1)[CH3:23].C([O-])([O-])=O.[Na+].[Na+]>O.O1CCOCC1.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]>[CH2:22]([C:24]1[O:25][C:26]2[C:32]([C:10]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:3](=[O:21])[N:2]([CH3:1])[CH:11]=3)=[CH:31][C:30]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:29][C:27]=2[CH:28]=1)[CH3:23]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 118022026HCID 118022026, compoundHCID 1238094992-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one

Product 1

HCID 118021500HCID 118021500, compoundYield 33%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a solution of 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one (82 mg, 286 umol) and the title compound from Step 1 (100 mg, 286 umol) in H2O (2 mL) and dioxane (20 mL) was added Pd(dppf)Cl2 (21 mg, 28.6 umol, 0.10 Eq) and Na2CO3 (61 mg, 572 umol). The mixture was degassed with nitrogen and heated to 90° C. for 4 h. It was then cooled to rt and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (PE: EA=3:1 to 1:1) followed by prep-HPLC to afford the title compound (35.57 mg, 33%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.56 (d, J=7.2 Hz, 1H), 8.19 (d, J=1.6 Hz, 1H), 7.83 (d, J=1.6 Hz, 1H), 7.60-7.57 (m, 2H), 7.29-7.27 (m, 2H), 6.60 (s, 1H), 3.73 (s, 3H), 3.15 (s, 3H) 2.75 (q, J=7.2 Hz, 2H), 1.28 (t, J=7.2 Hz, 3H). LCMS: 382.0 (M+H+)

Workup

  1. customThe mixture was degassed with nitrogen
  2. temperatureIt was then cooled to rt
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (PE: EA=3:1 to 1:1)

Sources & evidence

ORD record
ord-2209b7e10a804565a3be2907a16db48e
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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