Potassium Phosphate, Tribasic → (S)-4-(2-((5-((2-Oxopyrrolidin-3-yl)amino)-1,3,4-oxadiazol-2-yl)methyl)benzo[d]thiazol-6-yl)benzamide

HRID 1754258ノート

反応式

HRID 1754258 の反応式
[C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].Br[C:14]1[CH:35]=[CH:34][C:17]2[N:18]=[C:19]([CH2:21][C:22]3[O:26][C:25]([NH:27][C@H:28]4[CH2:32][CH2:31][NH:30][C:29]4=[O:33])=[N:24][N:23]=3)[S:20][C:16]=2[CH:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.CO.[Pd]>[O:33]=[C:29]1[C@@H:28]([NH:27][C:25]2[O:26][C:22]([CH2:21][C:19]3[S:20][C:16]4[CH:15]=[C:14]([C:7]5[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[CH:5][CH:6]=5)[CH:35]=[CH:34][C:17]=4[N:18]=3)=[N:23][N:24]=2)[CH2:32][CH2:31][NH:30]1

参加物

9

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27378114-Aminocarbonylphenylboronic acidHCID 90047760(S)-3-((5-((6-Bromobenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)amino)pyrrolidin-2-one

生成物 1

HCID 90047667(S)-4-(2-((5-((2-Oxopyrrolidin-3-yl)amino)-1,3,4-oxadiazol-2-yl)methyl)benzo[d]thiazol-6-yl)benzamide収率 31.9%

試薬・触媒・溶媒 5

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
125 °C

実験手順

To a microwave vial containing SiliaCat DPP-Pd (150 mg, 0.041 mmol) and (4-carbamoylphenyl)boronic acid (65 mg, 0.40 mmol) were added Compound 51b (104 mg, 0.260 mmol) dissolved in dioxane (2.5 mL) followed by K3PO4 (138 mg, 0.79 mmol) dissolved in water (0.3 mL) and the reaction mixture was heated in a microwave reactor at 125° C. for 1.5 h. The reaction mixture was allowed to cool to rt then diluted with a mixture of DCM and MeOH, filtered and concentrated under reduced pressure. The residue was purified on silica gel eluting with 0 to 15% MeOH/DCM to give Compound 51c (36 mg, 31% yield) as a pale brown solid. LCMS=1.33 min using analytical method (B), 435.1 (M+H). 1H NMR (400 MHz CDCl3 containing CD3OD) δ 8.05 (d, J=1.5 Hz, 1H), 7.98 (d, J=8.5 Hz, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.69 (dd, J=8.5, 1.8 Hz, 1H), 7.65 (d, J=8.5 Hz, 2H), 4.54 (s, 1H), 4.23 (dd, J=10.5, 8.3 Hz, 1H), 3.36-3.31 (m, 1H), 2.68-2.59 (m, 1H), 2.03 (dq, J=12.5, 9.8 Hz, 1H).

後処理

  1. temperatureto cool to rt
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified on silica gel eluting with 0 to 15% MeOH/DCM

出典と根拠

ORDレコード
ord-bd3ba0e94b354749bebceb24e282a52f
出典データセット
uspto-grants-2015_10
特許番号
US09169240B2

反応ノート

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