Dimethylformamide → (S)-7-((3-methyloxetan-3-yl)ethynyl)-3-(neopentyloxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 1970316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1970316
Br[C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[N:10][CH:11]=[C:12]([O:21][CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:13]=3)[O:8][C:5]2=[CH:6][CH:7]=1.CN(C=O)C.C(NC(C)C)(C)C.C[Si](C)(C)[C:41]#[C:42][C:43]1([CH3:47])[CH2:46][O:45][CH2:44]1>[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:47][C:43]1([C:42]#[C:41][C:2]2[CH:3]=[C:4]3[C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:14]4[C:9](=[N:10][CH:11]=[C:12]([O:21][CH2:22][C:23]([CH3:26])([CH3:24])[CH3:25])[CH:13]=4)[O:8][C:5]3=[CH:6][CH:7]=2)[CH2:46][O:45][CH2:44]1

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 58547788Trimethyl((3-methyloxetan-3-yl)ethynyl)silaneHCID 67240631(S)-7-bromo-3-(neopentyloxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Produkt 1

HCID 58466249(S)-7-((3-methyloxetan-3-yl)ethynyl)-3-(neopentyloxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 83717Copper iodideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A sealable tube was charged with (S)-7-bromo-3-(neopentyloxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (75 mg, 0.179 mmol), copper iodide (3.38 mg, 0.018 mmol), tetrakis(triphenylphosphine)palladium (20.53 mg, 0.018 mmol). To this mixture was added DMF (355 μL, 0.178 mmol), diisopropylamine (498 μL, 3.55 mmol) and trimethyl((3-methyloxetan-3-yl)ethynyl)silane (90 mg, 0.533 mmol). The tube was flushed with argon, sealed and heated to 90° C. for 12 hours. The reaction was diluted with water (100 mL) and poured into a separatory funnel containing ethyl acetate (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (12 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-7-((3-methyloxetan-3-yl)ethynyl)-3-(neopentyloxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a yellow solid.

Aufarbeitung

  1. customThe tube was flushed with argon
  2. customsealed
  3. additionThe reaction was diluted with water (100 mL)
  4. additionpoured into a separatory funnel
  5. additioncontaining ethyl acetate (50 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  8. washThe combined organic layers were washed with water
  9. dry with materialbrine, dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a brown oil that
  13. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (12 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

Quellen und Nachweise

ORD-Eintrag
ord-0d8359d04f9d4b41b50d7429499e4fe7
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08426447B2

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