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 1754258노트

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HRID 1754258 반응식
[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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 5

HCID 23938Palladium촉매HCID 887Methanol용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
125 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-bd3ba0e94b354749bebceb24e282a52f
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169240B2

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