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Sodium Carbonate → N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide

HRID 570136
ノート
印刷プレビュー

反応式

HRID 570136 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17](B3OC(C)(C)C(C)(C)O3)=[C:11]3[O:12][CH2:13][CH2:14][CH:15]([CH3:16])[N:10]3[N:9]=2)=[CH:4][CH:3]=1.Br[C:28]1[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:17]([C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35](=[O:38])[CH2:36][CH3:37])[CH:29]=3)=[C:11]3[O:12][CH2:13][CH2:14][CH:15]([CH3:16])[N:10]3[N:9]=2)=[CH:6][CH:7]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 67073822N-(4-bromopyridin-2-yl)propanamideHCID 894883172-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

生成物 1

HCID 89488349N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide収率 23.5%

試薬・触媒・溶媒 2

HCID 11556747
Bis(tricyclohexylphosphine)palladium(II) Dichloride
触媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

150 mg of 2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (0.419 mmol, 1.1 eq.) and 87 mg of N-(4-bromopyridin-2-yl)propanamide (0.381 mmol, 1 eq.) are dissolved in 1.5 ml of 1,4-dioxane. To this solution are added 22 mg of bis(tricyclohexylphosphine)-palladium(II)dichloride (0.03 mmol, 0.08 eq) and a aqueous solution of Na2CO3 (5 eq, 0.952 ml). The reaction mixture is flushed for 5 mins with argon and then sealed. Next the mixture is heated for 15 mins at 120° C. in the microwave (CEM Explorer). After cooling, the reaction mixture is diluted with EtOAc and washed with water. The combined organic phase are dried over Na2SO4 and concentrated in vacuo. The crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate). 34 mg (21%) of N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide are obtained.

後処理

  1. customThe reaction mixture is flushed for 5 mins with argon
  2. customsealed
  3. temperatureAfter cooling
  4. additionthe reaction mixture is diluted with EtOAc
  5. washwashed with water
  6. dry with materialThe combined organic phase are dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

出典と根拠

ORDレコード
ord-fb6540000e2b499aa0536deabc6de2b9
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09023844B2

反応ノート

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