Hydrochloric Acid → tert-Butyl 3-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)benzyl(2-methoxyethyl)carbamate

HRID 1710919노트

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HRID 1710919 반응식
[F:1][C:2]1[CH:36]=[C:35]([N+:37]([O-])=O)[CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:15]=[C:16]([CH:30]=[CH:31][CH:32]=3)[CH2:17][N:18]([CH2:26][CH2:27][O:28][CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[S:13][C:6]=12.[BH4-].[Na+].Cl>C1COCC1.CO.Cl[Ni]Cl>[NH2:37][C:35]1[CH:34]=[CH:33][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[CH:11]=[C:12]([C:14]4[CH:15]=[C:16]([CH:30]=[CH:31][CH:32]=4)[CH2:17][N:18]([CH2:26][CH2:27][O:28][CH3:29])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[S:13][C:6]=23)=[C:2]([F:1])[CH:36]=1

참가 물질

7

반응물 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 59457707tert-Butyl 3-(7-(2-fluoro-4-nitrophenoxy)thieno{3,2-b}pyridine-2-yl)benzyl(2-methoxyethyl)carbamate

생성물 1

HCID 59457715tert-Butyl 3-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)benzyl(2-methoxyethyl)carbamate수율 74.8%

시약·촉매·용매 3

HCID 24385Nickel Dichloride촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a solution of 73 (347 mg, 0.6 mmol) in THF (4 mL) and MeOH (2 mL), NiCl2 (372 mg, 1.6 mmol) was added and the solution was cooled to 0° C. NaBH4 (95 mg, 2.5 mmol) was added portion wise. After 20 minutes, the reaction was treated with 2 M HCl and solvents were removed under reduced pressure. The concentrated mixture was basified to pH 10 with ammonium hydroxide solution and the mixture was extracted with EtOAc, the extract was dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel column chromatography, eluent EtOAc, to afford the title compound 74 (235 mg, 72% yield) as a white solid. 1H NMR (DMSO) δ (ppm): 8.47 (d, J=5.6 Hz, 1H), 7.97 (s, 1H), 7.77 (d, J=7.2 Hz, 1H), 7.70 (s, 1H), 7.48 (t, J=7.6 Hz, 1H), 6.56-6.51 (m, 2H), 6.44 (dd, J=6.3 Hz, 1H), 5.54 (s, 2H), 4.84 (s, 2H), 3.43 (s, 2H), 3.23 (s, 3H), 2.50 (q, J=2.2 Hz, 4H), 1.46-1.35 (m, 9H).

후처리

  1. customwere removed under reduced pressure
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialthe extract was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography, eluent EtOAc

출처 및 근거

ORD 기록
ord-835713bb6fe74775978252cd4cc4f2d6
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07790729B2

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