Ammonium Chloride → N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-yl)acetamide

HRID 1915924ノート

反応式

HRID 1915924 の反応式
[CH3:1][C:2]1([NH:18][C:19](=[O:21])[CH3:20])[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-])=O)[CH2:4][CH2:3]1.[Cl-].[NH4+]>CCO.O.[Fe]>[NH2:15][C:10]1[CH:11]=[N:12][N:13]([CH3:14])[C:9]=1[N:5]1[CH2:6][CH2:7][CH2:8][C:2]([NH:18][C:19](=[O:21])[CH3:20])([CH3:1])[CH2:3][CH2:4]1

参加物

6

反応物 2

HCID 25517Ammonium ChlorideHCID 86680019HCID 86680019、化合物

生成物 1

HCID 86680124N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-yl)acetamide

試薬・触媒・溶媒 3

HCID 23925Iron触媒HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of N-(4-methyl-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-4-yl)acetamide (330 mg, 1.11 mmol) in a mixture of EtOH (25 mL) and water (2.5 mL) was added ammonium chloride (300 mg, 5.55 mmol) and iron powder (250 mg, 4.44 mmol). The reaction mixture was heated at 100° C. for 2 hr before being cooled, filtered through Celite® and concentrated under reduced pressure. The residue was partitioned between water (20 mL) and DCM (40 mL) and the organic layer was separated, washed with brine (20 mL), passed through a phase separation cartridge and concentrated under reduced pressure to give N-(1-(4-amino-1-methyl-1H-pyrazol-5-yl)-4-methylazepan-4-yl)acetamide as a brown solid which was used without further purification. Following the procedure for Example 149 using this intermediate and 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)-thiazole-4-carboxylic acid gave 378 as an off-white foam (54 mg, 19% over three steps). 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.86 (s, 1H), 7.39-7.29 (m, 1H), 7.07-6.99 (m, 2H), 6.15 (s, 2H), 5.38 (s, 1H), 3.74 (s, 3H), 3.30-3.18 (m, 4H), 3.12 (ddd, J=13.6, 6.6, 3.1 Hz, 1H), 2.30-2.19 (m, 2H), 2.00-1.72 (m, 6H), 1.45 (s, 3H). LCMS (ES+) m/z 504 (M+1)

後処理

  1. temperaturebefore being cooled
  2. filtrationfiltered through Celite®
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between water (20 mL) and DCM (40 mL)
  5. customthe organic layer was separated
  6. washwashed with brine (20 mL)
  7. custompassed through a phase separation cartridge
  8. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-b620192cd6fc49af9a071ae4c8831b0a
出典データセット
uspto-grants-2013_12
特許番号
US08614206B2

反応ノート

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