Potassium Phosphate, Tribasic → US10023592, Example 255

HRID 575734Notes

Reaction equation

HRID 575734 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([NH:12][S:13]([CH2:16][CH3:17])(=[O:15])=[O:14])=[CH:8][C:7]=2B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.Br[C:28]1[C:29]2[CH:38]=[CH:37][O:36][C:30]=2[C:31](=[O:35])[N:32]([CH3:34])[CH:33]=1.[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[CH:11]=[CH:10][C:9]([NH:12][S:13]([CH2:16][CH3:17])(=[O:14])=[O:15])=[CH:8][C:7]=2[C:28]2[C:29]3[CH:38]=[CH:37][O:36][C:30]=3[C:31](=[O:35])[N:32]([CH3:34])[CH:33]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180214004-Bromo-6-methylfuro[2,3-c]pyridin-7-oneHCID 123718098N-(4-(Cyclopropylmethoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanesulfonamide

Product 1

HCID 118021422US10023592, Example 255Yield 16%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

A mixture of N-[4-(cyclopropylmethoxy)-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethane-1-sulfonamide (138 mg, 0.38 mmol), 4-bromo-6-methyl-6H,7H-furo[2,3-c]pyridin-7-one (75 mg, 0.33 mmol), K3PO4 (175 mg, 0.83 mmol), Pd(dppf)Cl2 (24 mg, 10%) in dioxane (2.2 mL) and H2O (200 uL) was bubbled with nitrogen for 5 min. The sealed vial was stirred at 70° C. for 4 h. After the reaction mixture was filtered through a short plug of celite, the celite plug was washed with EtOAc (15 mL). The filtrate was washed with water and brine; the organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford a tan residue. The resulting residue was purified by prep-HPLC to afford the title compound (21 mg, 16%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.15-0.28 (m, 2H) 0.35-0.52 (m, 2H) 0.95-1.13 (m, 1H) 1.14-1.26 (m, 3H) 2.98-3.09 (m, 2H) 3.57-3.65 (m, 3H) 3.77-3.87 (m, 2H) 7.04-7.22 (m, 3H) 7.55-7.64 (m, 1H) 8.05-8.17 (m, 1H) 9.49-9.57 (m, 1H). LCMS (M+H)+=403.

Workup

  1. customwas bubbled with nitrogen for 5 min
  2. filtrationAfter the reaction mixture was filtered through a short plug of celite
  3. washthe celite plug was washed with EtOAc (15 mL)
  4. washThe filtrate was washed with water and brine
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a tan residue
  9. customThe resulting residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-11de4febdea6419596d7bf080d1623c0
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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