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Sodium Carbonate → 2-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazole-4-carbonitrile

HRID 473977
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 473977
Br[C:2]1[S:6][C:5]([N:7]2[CH2:12][C@H:11]([CH3:13])[O:10][C@H:9]([CH3:14])[CH2:8]2)=[N:4][C:3]=1[C:15]#[N:16].[CH3:17][C:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[C:20]([CH3:27])[N:19]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.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>[CH3:14][C@H:9]1[O:10][C@@H:11]([CH3:13])[CH2:12][N:7]([C:5]2[S:6][C:2]([C:22]3[CH:21]=[C:20]([CH3:27])[N:19]=[C:18]([CH3:17])[CH:23]=3)=[C:3]([C:15]#[N:16])[N:4]=2)[CH2:8]1
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Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 23546910(2,6-Dimethylpyridin-4-yl)boronic acidHCID 672167795-Bromo-2-(cis-2,6-dimethyl-morpholin-4-yl)-thiazole-4-carbonitrile

Produkt 1

HCID 672165242-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazole-4-carbonitrileAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 19096565Water ethanolLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of Intermediate 3 (20 g, 66.18 mmol), 2,6-dimethylpyridine-4-boronic acid, pinacol ester ([325142-95-8], 20 g, 85.79 mmol), tetrakis(triphenylphosphine)palladium (4.59 g, 3.97 mmol), 1,4-dioxane (120 mL), sodium carbonate (21.04 g, 198.55 mmol) in ethanol/water 1/1 (120 mL) was stirred and heated under nitrogen atmosphere at 130° C. for 6 h. The solvent was evaporated. The residue was taken up in DCM and washed twice with water. The organic layer was separated, dried with MgSO4 and evaporated. The residue was purified by column chromatography on silica gel (eluent gradient from 100% DCM to 98/2 DCM/MeOH). The desired fractions were collected and evaporated. The resulting residue was recrystallized from DIPE/CH3CN, yielding 18.5 g (85%) of Intermediate 4, after drying overnight under vacuum at 50° C.

Aufarbeitung

  1. customThe solvent was evaporated
  2. washwashed twice with water
  3. customThe organic layer was separated
  4. dry with materialdried with MgSO4
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica gel (eluent gradient from 100% DCM to 98/2 DCM/MeOH)
  7. customThe desired fractions were collected
  8. customevaporated
  9. customThe resulting residue was recrystallized from DIPE/CH3CN

Quellen und Nachweise

ORD-Eintrag
ord-f365e2cdb89142419e38feabb3eed020
Quelldatensatz
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08637510B2

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