proline dl-form → (1aR,5aR)-2-(5-Methoxy-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid Ethyl Ester

HRID 1623921노트

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HRID 1623921 반응식
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:14][C@H:10]3[C:11]=2[NH:12][N:13]=1)=[O:5])[CH3:2].I[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][N:17]=1.N1CCCC1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>[Cu]I>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:14][C@H:10]3[C:11]=2[N:12]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][N:17]=2)[N:13]=1)=[O:5])[CH3:2]

참가 물질

6

반응물 4

HCID 614proline dl-formHCID 11430Potassium CarbonateHCID 70107332-Iodo-5-methoxypyridineHCID 589068031H-Cyclopropa[4,5]cyclopenta[1,2]pyrazole-3-carboxylic acid, 4,4a,5,5a-tetrahydro-, ethyl ester, (4aR,5aR)-

생성물 1

HCID 68182605(1aR,5aR)-2-(5-Methoxy-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic Acid Ethyl Ester수율 36.4%

시약·촉매·용매 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매

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온도
75 °C

실험 절차

A 20 mL scintillation vial was charged with (1aR,5aR)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester (492 mg, 2.56 mmol), 2-iodo-5-methoxypyridine (662 mg, 2.82 mmol), DL-proline (58.9 mg, 0.512 mmol), copper(I) iodide (48.7 mg, 0.256 mmol), and potassium carbonate (708 mg, 5.12 mmol). The vial was flushed with nitrogen, and added DMSO (15 mL). The reaction was stirred under nitrogen at 75° C. for 15 h. The reaction was filtered then purified by HPLC to provide the title compound (279 mg) as a white solid. LCMS m/z=300.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.45 (td, J=4.7, 3.3 Hz, 1H), 1.23 (td, J=8.0, 4.8 Hz, 1H), 1.39 (t, J=7.2 Hz, 3H), 2.21-2.27 (m, 1H), 2.77-2.82 (m, 1H), 2.85 (d, J=16.6 Hz, 1H), 2.97 (dd, J=16.6, 6.4 Hz, 1H), 3.90 (s, 3H), 4.38 (q, J=7.2 Hz, 2H), 7.34 (dd, J=8.8, 2.9 Hz, 1H), 7.98 (dd, J=9.0, 0.6 Hz, 1H), 8.13 (dd, J=3.0, 0.5 Hz, 1H).

후처리

  1. customThe vial was flushed with nitrogen
  2. additionadded DMSO (15 mL)
  3. filtrationThe reaction was filtered
  4. customthen purified by HPLC

출처 및 근거

ORD 기록
ord-8b1267976008428abed1f23340c02494
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778950B2

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