Potassium Phosphate, Tribasic → HCID 118022091, compound

HRID 575784Notes

Reaction equation

HRID 575784 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:13][S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.[CH3:19][N:20]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=[O:39].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:10]1([CH2:9][O:8][C:7]2[N:6]=[CH:5][C:4]([NH:13][S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])=[CH:3][C:2]=2[C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21](=[O:39])[N:20]([CH3:19])[CH:29]=2)[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 118021716HCID 118021716, compoundHCID 1238094992-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one

Product 1

HCID 118022091HCID 118022091, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-[5-bromo-6-(cyclopropylmethoxy)pyridin-3-yl]ethanesulfonamide (60 mg, 0.21 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one (77 mg, 0.23 mmol), Pd2(dba)3 (7 mg), XPhos (7 mg), and K3PO4 (111 mg, 0.51 mmol) in dioxane (1.2 mL) and water (140 uL) was purged with nitrogen, capped, and heated to 70° C. for 2 h. After the mixture was filtered through a short bed of celite, the filtrate was concentrated in vacuo and purified by prep-HPLC to afford the title compound (45 mg, 52%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.09-0.15 (m, 2H) 0.29-0.40 (m, 2H) 0.97-1.08 (m, 1H) 1.20-1.28 (m, 3H) 3.07-3.16 (m, 2H) 3.56 (s, 3H) 4.02-4.18 (m, 2H) 7.17-7.22 (m, 1H) 7.52 (s, 3H) 7.62-7.69 (m, 1H) 8.06-8.11 (m, 1H) 8.27-8.33 (m, 1H) 9.47-10.31 (m, 1H). LCMS (M+H)+=414.

Workup

  1. customwas purged with nitrogen
  2. customcapped
  3. filtrationAfter the mixture was filtered through a short bed of celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-5270b9e0f7ec4394b74555a3833379ae
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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