Water → (R)-N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

HRID 250051

반응식

HRID 250051 반응식
[CH2:1]([O:8][C:9]1[N:14]=[C:13]2[S:15][C:16]([N:18]=[C:19](SC)SC)=[N:17][C:12]2=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[NH2:26][CH2:27][C@@:28]1([OH:36])[CH:33]2[CH2:34][CH2:35][N:30]([CH2:31][CH2:32]2)[CH2:29]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH2:1]([O:8][C:9]1[N:14]=[C:13]2[S:15][C:16]([NH:18][C:19]3[O:36][C@:28]4([CH2:27][N:26]=3)[CH:33]3[CH2:34][CH2:35][N:30]([CH2:31][CH2:32]3)[CH2:29]4)=[N:17][C:12]2=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 58088081Carbonimidodithioic acid, N-[5-(phenylmethoxy)thiazolo[5,4-b]pyridin-2-yl]-, dimethyl esterHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

생성물 1

HCID 58088124(R)-N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine수율 67%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

A mixture of dimethyl 5-(benzyloxy)thiazolo[5,4-b]pyridin-2-ylcarbonimidodithioate (500 mg, 1.38 mmol), (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (317 mg, 1.38 mmol) and cesium carbonate (1.0 g, 3.07 mmol) in DMF (7 mL) was heated to 100° C. for 2 hours. The reaction mixture was cooled to ambient temperature, poured into water and extracted with chloroform (4×). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The mixture was purified by silica gel chromatography (2-20% [9:1 methanol:ammonium hydroxide]-chloroform) to afford (R)—N-(5-(benzyloxy)thiazolo[5,4-b]pyridin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (390 mg, 67% yield). 1H NMR (500 MHz, CDCl3) δ ppm 9.18 (br. s., 1 H) 7.76 (d, J=8.85 Hz, 1 H) 7.50 (d, J=7.32 Hz, 2 H) 7.41 (t, J=7.32 Hz, 2 H) 7.32-7.37 (m, 1 H) 5.42 (s, 2 H) 4.02 (d, J=9.46 Hz, 1 H) 3.68 (d, J=9.46 Hz, 1 H) 3.37-3.44 (m, 1 H) 2.75-3.06 (m, 5 H) 2.13-2.25 (m, 2 H) 1.73-1.82 (m, 1 H) 1.49-1.70 (m, 3 H). MS (LC/MS) R.T.=1.69; [M+H]+=421.98.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionextracted with chloroform (4×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe mixture was purified by silica gel chromatography (2-20% [9:1 methanol:ammonium hydroxide]-chloroform)

출처 및 근거

ORD 기록
ord-d0e686abd6c5480da9990ccb40e94897
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863291B2

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