Dichloromethane → Ethyl 1-amino-4-[3-(benzyloxy)phenyl]-5-cyano-1H-pyrrole-2-carboxylate

HRID 1972810노트

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HRID 1972810 반응식
[NH2:1][N:2]1[C:6]([C:7]#[N:8])=[C:5](Br)[CH:4]=[C:3]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.ClCCl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[NH2:1][N:2]1[C:6]([C:7]#[N:8])=[C:5]([C:27]2[CH:26]=[CH:25][CH:24]=[C:23]([O:22][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:28]=2)[CH:4]=[C:3]1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

참가 물질

6

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 58529285Ethyl 1-amino-4-bromo-5-cyano-1H-pyrrole-2-carboxylate

생성물 1

HCID 58529622Ethyl 1-amino-4-[3-(benzyloxy)phenyl]-5-cyano-1H-pyrrole-2-carboxylate수율 50%

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
80 °C

실험 절차

To a stirred solution of ethyl 1-amino-4-bromo-5-cyano-1H-pyrrole-2-carboxylate (1.43 g, 5.55 mmol), 4-benzyloxybenzeneboronic acid (3.80 g, 16.7 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II) complex with dichloromethane (453 mg, 0.56 mmol) in degassed DME (41 mL) was added aqueous Na2CO3 solution (2 M, 8.3 mL). The reaction was heated (80° C.) for 17 h and then cooled to rt. The reaction was filtered through a pad of Celite® and the filter cake was rinsed well with ethyl acetate. The filtrate was partitioned between ethyl acetate (100 mL) and water (100 mL) and the layers were separated. The organic phase was further washed with water (75 mL), brine, was dried (Na2SO4), and concentrated. The crude material was purified by flash chromatography on silica gel using a gradient of 10 to 20% ethyl acetate in hexanes to afford 1.0 g (50%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 7.47-7.43 (m, 2 H), 7.41-7.25 (m, 6 H), 7.18 (s, 1 H), 7.02-6.97 (m, 1 H), 6.55 (s, 2 H), 5.15 (s, 2 H), 4.31 (q, 2 H), 1.33 (t, 3 H); ES-MS m/z 362.02 [M+H]+, HPLC RT (min) 3.38.

후처리

  1. temperaturecooled to rt
  2. filtrationThe reaction was filtered through a pad of Celite®
  3. washthe filter cake was rinsed well with ethyl acetate
  4. customThe filtrate was partitioned between ethyl acetate (100 mL) and water (100 mL)
  5. customthe layers were separated
  6. washThe organic phase was further washed with water (75 mL), brine
  7. dry with materialwas dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by flash chromatography on silica gel using a gradient of 10 to 20% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-11d6e496273b4aad8030598458a90c57
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431695B2

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