tert-Butyl methyl ether → HCID 178429374、化合物

HRID 707309ノート

反応式

HRID 707309 の反応式
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16](=[O:27])[C:17]([C:20]2[C:21](Cl)=[N:22][CH:23]=[CH:24][CH:25]=2)([CH3:19])[CH3:18])[CH2:12]1.CC(C)([O-])C.[Na+].C(OC)(C)(C)C>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([N:15]2[C:21]3=[N:22][CH:23]=[CH:24][CH:25]=[C:20]3[C:17]([CH3:19])([CH3:18])[C:16]2=[O:27])[CH2:12]1

参加物

4

反応物 3

HCID 15413tert-Butyl methyl etherHCID 23676156Sodium t-butoxideHCID 178454574HCID 178454574、化合物

生成物 1

HCID 178429374HCID 178429374、化合物収率 58.6%

反応条件

温度
80 °C

実験手順

N-(Trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-2-(2-chloropyridin-3-yl)-2-methylpropanamide (0.086 g, 0.216 mmol), sodium t-butoxide (0.040 g, 0.416 mmol), and chloro(2-dicyclohexylphosphino-2′,6′-di-1-propoxy-1,1′-biphenyl)[2-(2-aminoethyl-phenyl)]palladium(ii), methyl t-butyl ether adduct (0.010 g, 0.012 mmol) were sealed in a microwave vessel under argon. Dry, sparged dioxane (0.5 mL) was added and the reaction heated at 80° C. After 35 minutes the mixture was cooled and partitioned between ethyl acetate (100 mL), water (100 mL) and saturated sodium bicarbonate (10 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) followed by reverse phase HPLC gave 1-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (0.0481 g, 0.126 mmol, 58.6% yield) as an off white solid. M+1: 365.1. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.39 (s, 6 H) 2.45 (m, J=3.36 Hz, 2 H) 3.38-3.63 (m, 2 H) 4.51-4.72 (m, 1 H) 5.30 (quin, J=8.66 Hz, 1 H) 5.59-5.80 (m, 1 H) 6.97 (dd, J=7.16, 5.26 Hz, 1 H) 7.04-7.16 (m, 1 H) 7.21-7.35 (m, 1 H) 7.43 (dd, J=7.31, 1.61 Hz, 1 H) 7.59 (dd, J=10.52, 8.33 Hz, 2 H) 8.19 (dd, J=5.19, 1.53 Hz, 1 H).

後処理

  1. customDry
  2. customsparged dioxane (0.5 mL)
  3. additionwas added
  4. temperatureAfter 35 minutes the mixture was cooled
  5. custompartitioned between ethyl acetate (100 mL), water (100 mL) and saturated sodium bicarbonate (10 mL)
  6. dry with materialThe organic phase was dried with magnesium sulfate
  7. customevaporated to dryness under reduced pressure
  8. customPurification

出典と根拠

ORDレコード
ord-cf51434cec7440869ec1f6d1e542eaae
出典データセット
uspto-grants-2015_11
特許番号
US09174992B2

反応ノート

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