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

HRID 500779ノート

反応式

HRID 500779 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 24385Nickel Dichloride触媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-397102216ad84458a474def08d2075c3
出典データセット
uspto-grants-2010_08
特許番号
US07772247B2

反応ノート

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