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 1776426ノート

反応式

HRID 1776426 の反応式
[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

参加物

5

反応物 3

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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-58d48d955dc344f4891745c4575e7fbd
出典データセット
uspto-grants-2016_02
特許番号
US09265763B2

反応ノート

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