Potassium Phosphate, Tribasic → US10023592, Example 265

HRID 518484Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 518484
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])=[CH:8][C:7]=2B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.Br[C:27]1[C:28]2[CH:37]=[C:36]([C:38]([NH2:40])=[O:39])[S:35][C:29]=2[C:30](=[O:34])[N:31]([CH3:33])[CH:32]=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]([S:12]([CH2:15][CH3:16])(=[O:13])=[O:14])=[CH:8][C:7]=2[C:27]2[C:28]3[CH:37]=[C:36]([C:38]([NH2:40])=[O:39])[S:35][C:29]=3[C:30](=[O:34])[N:31]([CH3:33])[CH:32]=2)[CH2:2][CH2:3]1

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 896575182-[2-(Cyclopropylmethoxy)-5-(ethylsulfonyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 1180216454-Bromo-6-methyl-7-oxothieno[2,3-c]pyridine-2-carboxamide

Produkt 1

HCID 118021522US10023592, Example 265Ausbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A mixture of 2-[2-(cyclopropylmethoxy)-5-ethylsulfonylphenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (77 mg, 0.22 mmol), 4-bromo-6-methyl-7-oxothieno[2,3-c]pyridine-2-carboxamide (50 mg, 0.18 mmol), K3PO4 (93 mg, 0.44 mmol), Pd(dppf)Cl2 (13 mg, 10%) in dioxane/H2O (1.6 mL/160 uL) was bubbled with nitrogen for 5 min. The sealed vial was stirred at 65° C. for 3 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 (20 mg, 26%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.20 (m, 2H) 0.36 (m, 2H) 0.98 (m, 1H) 1.14 (m, 3H) 3.21-3.31 (m, 2H) 3.61 (s, 3H) 3.98 (m, 2H) 7.38 (d, J=8.6 Hz, 1H) 7.65-7.75 (m, 3H) 7.78 (d, J=2.0 Hz, 1H) 7.91 (dd, J=8.6, 2.0 Hz, 1H) 8.24 (s, 1H). LCMS (M+H)+=447.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-e5973e6aabef49479f43c9adfdb402d1
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115114B2

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