Dichloromethane → [5-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

HRID 1625427Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1625427
[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][C:9]1[S:10][C:11](Br)=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C(OC([N:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24]1)=O)(C)(C)C.ClCCl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>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]>[C:1]([O:5][C:6](=[O:15])[NH:7][CH2:8][C:9]1[S:10][C:11]([C:25]2[C:26]3[C:27](=[N:28][CH:29]=[CH:30][CH:31]=3)[NH:23][CH:24]=2)=[CH:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2779810tert-Butyl ((5-bromothiophen-2-yl)methyl)carbamateHCID 53217196tert-Butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate

Produkt 1

HCID 59362564[5-(1H-Pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Into a vial was dissolved (5-bromo-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester (115 mg, 0.000394 mol; Maybridge), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (119 mg, 0.000346 mol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (28 mg, 0.000034 mol; Strem) in 1,4-dioxane (6.0 mL, 0.077 mol; Acros). To this was added 2.0 M of sodium carbonate in water (1.5 mL). The reaction was purged with Ar and sealed. The reaction was heated at 110° C. under an atmosphere of Argon for 2 hours. The reaction was diluted with methylene chloride and washed with water. The organic layer was dried with magnesium sulfate, filtered and evaporated. The residue was taken up in DMSO and purified by preparative HPLC to yield the title compound in 33.4 mg yield (22%) as the TFA salt. MS m/z=330.15 (M+1). 1H NMR (400 MHz, CDCl3)™ ppm 13.919 (s, 1H) 8.703 (dd, J=7.9, 1.1 Hz, 1H) 8.246 (dd, J=5.7, 1.0 Hz, 1H) 7.676 (d, J=1.7 Hz, 1H) 7.464 (dd, J=7.9, 5.8 Hz, 1H) 7.111 (d, J=3.6 Hz, 1H) 6.985 (d, J=3.6 Hz, 1H) 4.981 (s (br), 1H) 4.508 (d, J=5.7 Hz, 2H) 1.485 (s, 9H).

Aufarbeitung

  1. customThe reaction was purged with Ar
  2. customsealed
  3. additionThe reaction was diluted with methylene chloride
  4. washwashed with water
  5. dry with materialThe organic layer was dried with magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-53d7033676b64f6080220e8396edb294
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08778977B2

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