Potassium Phosphate, Tribasic → HCID 118021631, compound

HRID 518410Notes

Reaction equation

HRID 518410 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[C:7](I)=[N:8][C:9]([S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:10][CH:11]=2)[CH2:3][CH2:2]1.[CH3:18][N:19]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]1=[O:38].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[CH:1]1([CH2:4][O:5][C:6]2[C:7]([C:27]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20](=[O:38])[N:19]([CH3:18])[CH:28]=3)=[N:8][C:9]([S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:10][CH:11]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 118021993HCID 118021993, compoundHCID 1238094992-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one

Product 1

HCID 118021631HCID 118021631, compoundYield 33.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of the title compound from Step 6 (45 mg, 0.12 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one (50 mg, 0.16 mmol) in dioxane (2.5 mL) and H2O (0.5 mL) was added Pd(dppf)Cl2 (9 mg, 0.013 mmol) and K3PO4 (86 mg, 0.4 mmol) in one portion at r.t. under N2. The mixture was stirred for 12 hours at 90° C. under N2. Water (15 mL) was added and the mixture was extracted with DCM (30 mL×3). The combined organic phases were dried over Na2SO4, filtered, concentrated under reduced pressure. The residue was purified by prep-HPLC to give the title compound (16 mg, yield: 32%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.52 (d, J=7.6 Hz, 1H), 8.11 (d, J=8.8 Hz 1H), 7.61-7.56 (m, 1H), 7.53-7.49 (m, 1H), 7.42 (d, J=8.8 Hz 1H), 7.38 (s, 1H), 7.34 (d, J=7.6 Hz 1H), 3.92 (d, J=7.2 Hz 2H), 3.68 (s, 3H), 3.41 (q, J=6.8 Hz, 2H), 1.33 (t, 3H), 1.08-1.02 (m, 1H), 0.54-0.48 (m, 2H), 0.22-0.21 (m, 2H). LCMS: 399.1 (M+1)+

Workup

  1. extractionthe mixture was extracted with DCM (30 mL×3)
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-29d4707ff86d427f8cbf9fe24f60fe2b
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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