Cesium carbonate → (R)-N-(6-phenoxypyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine

HRID 1875926노트

반응식

HRID 1875926 반응식
Cl.Cl.[NH2:3][CH2:4][C@@:5]1([OH:13])[CH:10]2[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]2)[CH2:6]1.C([O-])([O-])=O.[Cs+].[Cs+].[N:20]([C:23]1[CH:28]=[C:27]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:26]=[CH:25][N:24]=1)=[C:21]=S.C(N=C=NC(C)C)(C)C>CN(C)C=O>[O:29]([C:27]1[N:26]=[CH:25][N:24]=[C:23]([NH:20][C:21]2[O:13][C@:5]3([CH2:4][N:3]=2)[CH:10]2[CH2:9][CH2:8][N:7]([CH2:12][CH2:11]2)[CH2:6]3)[CH:28]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 12734DiisopropylcarbodiimideHCID 574765674-Isothiocyanato-6-phenoxypyrimidineHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

생성물 1

HCID 58088172(R)-N-(6-phenoxypyrimidin-4-yl)-4H-1'-azaspiro[oxazole-5,3'-bicyclo[2.2.2]octan]-2-amine수율 97%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.170 g, 0.742 mmol) in N,N-dimethylformamide (20 mL) was added Cs2CO3 (0.604 g, 1.854 mmol) and 4-isothiocyanato-6-phenoxypyrimidine (0.17 g, 0.742 mmol). The suspension was stirred at room temperature for 30 minutes. N,N′-diisopropylcarbodiimide (0.347 mL, 2.225 mmol) was then added and the mixture was continued to stir at room temperature for 18 hours. The mixture was concentrated and purified by silica gel chromatography (5-25% 9:1 methanol:ammonium hydroxide-ethyl acetate) to afford (R)—N-(6-phenoxypyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.21 g, 0.72 mmol, 48.2% yield) as a pale yellow solid. 1H NMR (500 MHz, MeOD) δ ppm 8.43 (1H, s), 7.47 (2H, t), 7.30 (1H, t), 7.16 (2H, d), 6.21 (1H, br. s.), 4.03 (1H, d), 3.72 (1H, d), 3.22 (1H, d), 3.11 (1H, d), 2.73-2.99 (4H, m), 2.00-2.18 (2H, m), 1.54-1.88 (3H, m). LCMS R.T.=1.46; [M+H]+=352.19.

후처리

  1. stirringto stir at room temperature for 18 hours
  2. concentrationThe mixture was concentrated
  3. custompurified by silica gel chromatography (5-25% 9:1 methanol:ammonium hydroxide-ethyl acetate)

출처 및 근거

ORD 기록
ord-24109fdf3bbd40a2b27a7939ce63a46c
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309577B2

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