Potassium Phosphate, Tribasic → US10023592, Example 257

HRID 575742Notes

Reaction equation

HRID 575742 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[N: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[N: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

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 1180214004-Bromo-6-methylfuro[2,3-c]pyridin-7-oneHCID 124023001N-[6-(cyclopropylmethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]ethanesulfonamide

Product 1

HCID 118022711US10023592, Example 257Yield 48%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

A mixture of N-[6-(cyclopropylmethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]ethanesulfonamide (145 mg, 0.38 mmol), 4-bromo-6-methyl-6H,7H-furo[2,3-c]pyridin-7-one (25 mg, 0.11 mmol), K3PO4 (58 mg, 0.28 mmol), Pd(dppf)Cl2 (8 mg, 10%) in dioxane/H2O (1 mL/100 uL) was bubbled with nitrogen for 5 min. The sealed vial was stirred at 65° C. for 12 h. 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, 48%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.23-0.32 (m, 2H) 0.41-0.52 (m, 2H) 1.08-1.19 (m, 1H) 1.20-1.29 (m, 3H) 3.05-3.16 (m, 2H) 3.58-3.63 (m, 3H) 3.64-3.66 (m, 1H) 4.08-4.17 (m, 2H) 6.72-6.82 (m, 1H) 7.58-7.65 (m, 1H) 7.67-7.73 (m, 1H) 7.95-8.06 (m, 1H) 8.10-8.18 (m, 1H) 9.41-9.86 (m, 1H). LCMS (M+H)+=404.

Workup

  1. customwas bubbled with nitrogen for 5 min
  2. filtrationThe 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-4281409a172e4b8fb5fde28de343c75b
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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