Potassium Carbonate → {2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-8-(pyridin-4-yl)-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-7-yl}methanol

HRID 1776426Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776426
[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:19]=[C:18]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=3)[C:17]([OH:27])=[CH:16][N:15]=2)=[N:6]1.Br[CH2:33][CH:34](O)[CH2:35][OH:36].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:1][C:2]1[CH:31]=[CH:30][CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:14]2[N:15]=[CH:16][C:17]3[O:27][CH2:33][CH:34]([CH2:35][OH:36])[N:20]([C:21]4[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=4)[C:18]=3[N:19]=2)=[N:6]1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 208273-Bromo-1,2-propanediolHCID 1362713042-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol

Produkt 1

HCID 86732452{2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-8-(pyridin-4-yl)-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-7-yl}methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

25 mg of 2-[1-(2-fluorobenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol (3-3, 0.061 mmol, 1. eq.), 28.2 mg of 3-bromopropane-1,2-diol (0.182 mmol, 3 eq.) and 41.9 mg of potassium carbonate (0.303 mmol, 5 eq.) were suspended in 470 μl of dry DMF under nitrogen atmosphere. The reaction mixture was stirred at 100° C. bath temperature for 18 hours. Then the mixture was partitioned between aqueous half saturated sodium chloride solution and ethyl acetate. The phases were separated and the aqueous layer was extracted once with ethyl acetate and once with dichloromethane/isopropanol 4:1. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by preparative TLC in dichloromethane/methanol 9:1 to yield 6.26 mg (0.01 mmol, 19.8%) of the analytically pure target compound.

Aufarbeitung

  1. customThen the mixture was partitioned between aqueous half saturated sodium chloride solution and ethyl acetate
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted once with ethyl acetate and once with dichloromethane/isopropanol 4:1
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative TLC in dichloromethane/methanol 9:1
  7. customto yield 6.26 mg (0.01 mmol, 19.8%) of the analytically pure target compound

Quellen und Nachweise

ORD-Eintrag
ord-58d48d955dc344f4891745c4575e7fbd
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265763B2

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