Diisopropylamine → N-methoxy-N-methyl-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-carboxamide

HRID 494829

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HRID 494829 반응식
[OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([N:8]([O:10][CH3:11])[CH3:9])=[O:7])=[CH:4][C:3]=1I.[CH2:15]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH3:24])[CH2:16][C:17]#[CH:18].CC1C=CC(P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C(NC(C)C)(C)C>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[CH3:11][O:10][N:8]([CH3:9])[C:6]([C:5]1[CH:12]=[CH:13][C:2]2[O:1][C:17]([CH2:16][CH2:15][N:19]3[CH2:23][CH2:22][CH2:21][C@H:20]3[CH3:24])=[CH:18][C:3]=2[CH:4]=1)=[O:7]

참가 물질

8

반응물 4

HCID 7912DiisopropylamineHCID 13956Phosphine, tris(4-methylphenyl)-HCID 11367023(R)-1-(But-3-yn-1-yl)-2-methylpyrrolidineHCID 117712104-hydroxy-3-iodo-N-methoxy-N-methylbenzamide

생성물 1

HCID 11438480N-methoxy-N-methyl-2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-carboxamide수율 10.2%

시약·촉매·용매 3

HCID 83717Copper iodide촉매HCID 167845palladium(II) acetate촉매HCID 6342Acetonitrile용매

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온도
25 °C

실험 절차

The product from Example 71D (11.6 g, 37.77 mmol) in acetonitrile (50 mL) was treated sequentially with a 0.12M solution of the product from Example 68B (378 mL, 45.33 mmol), Pd(OAc)2 (0.254 g, 1.13 mmol), tris(4-methylphenyl)phosphine (0.518 g, 1.699 mmol), and diisopropyl amine (39.7 mL, 283.3 mmol). After stirring at 25° C. for 10 minutes, the mixture was treated with copper iodide (2.158 g, 11.33 mmol) and heated at 50° C. in an inert atmosphere for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified on silica gel using 95% DCM, 9.9% MeOH, 0.1% NH4OH to provide the title compound (1.22 g, 10.2% yield). 1HNMR (300MHz, CD3OD) δ 1.18 (d, 3H, J=6.1 Hz), 1.47 (m, 1H), 1.78 (m, 2H), 1.91-2.34 (m, 2H), 2.50 (m, 2H) 3.06 (m, 2H), 3.26 (m, 2H), 3.38 (s, 3H), 3.59 (s, 3H), 6.63 (s, 1H), 7.51 (q, 2H), 7.84 (1H); MS (ESI) m/z 317.2 (M+H)+.

후처리

  1. temperatureheated at 50° C. in an inert atmosphere for 18 hours
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified on silica gel using 95% DCM, 9.9% MeOH, 0.1% NH4OH

출처 및 근거

ORD 기록
ord-dc151b476a42447c9c038bff6c8daf99
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07538138B2

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