p-Toluenesulfonic acid → N-(5-(4-fluorophenylamino)-1,3-dimethyl-5,6,7,8-tetrahydro naphthalen-2-yl)-3,3-dimethylbutanamide

HRID 1662284ノート

反応式

HRID 1662284 の反応式
[CH3:1][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][C:7](=O)[C:6]=2[CH:5]=[C:4]([CH3:13])[C:3]=1[NH:14][C:15](=[O:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18].[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.CC1C=CC(S(O)(=O)=O)=CC=1.C([BH3-])#N.[Na+]>C1(C)C=CC=C(C)C=1>[F:22][C:23]1[CH:29]=[CH:28][C:26]([NH:27][CH:7]2[CH2:8][CH2:9][CH2:10][C:11]3[C:2]([CH3:1])=[C:3]([NH:14][C:15](=[O:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:4]([CH3:13])=[CH:5][C:6]2=3)=[CH:25][CH:24]=1

参加物

6

反応物 4

HCID 6101p-Toluenesulfonic acidHCID 97314-FluoroanilineHCID 5003444Sodium cyanoborohydrideHCID 59808904N-(1,3-dimethyl-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)-3,3-dimethylbutanamide

生成物 1

HCID 25000130N-(5-(4-fluorophenylamino)-1,3-dimethyl-5,6,7,8-tetrahydro naphthalen-2-yl)-3,3-dimethylbutanamide収率 38%

試薬・触媒・溶媒 1

HCID 7929M-Xylene溶媒

反応条件

温度
160 °C

実験手順

A mixture of N-(1,3-dimethyl-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)-3,3-dimethylbutanamide (150 mg, 0.52 mmol), 4-fluoroaniline (116 mg, 1.04 mmol), and pTSA (20 mg) in 20 ml of m-xylene was heated at 160° C. for 6 hours. The solvent was removed in vacuo, and the residue was dissolved in a mixture of methanol (10 ml) and acetic acid (2 ml). Sodium cyanoborohydride (49 mg, 0.78 mmol) was added, and the resulting mixture was stirred at room temperature for 2 hours. After neutralization with saturated sodium bicarbonate, the mixture was extracted with chloroform (×3). The organic layer were combined, dried over anhydrous Na2SO4 and evaporated to dryness in vacuo. The residue was purified by Biotage (hexane/EtOAc, 0-30%, 40 min) to give a white solid (75 mg, 38%). 1H-NMR δ (DMSO-d6, 500 MHz): 9.09 (brs, 1H, exchangeable with D2O), 7.00 (s, 1H), 6.89 (t, J=7.5 Hz, 2H), 6.65 (dd, J=5.7 and 7.5 Hz, 2H), 5.70 (brs, 1H, exchangeable with D2O), 4.45 (m, 1H), 2.61 (m, 1H), 2.51 (m, 1H), 2.20 (s, 2H), 2.06 (s, 3H), 1.99 (s, 3H), 1.84 (m, 1H), 1.73 (m, 3H), 1.04 (s, 9H). MS: 383 (M+1).

後処理

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in a mixture of methanol (10 ml) and acetic acid (2 ml)
  3. extractionAfter neutralization with saturated sodium bicarbonate, the mixture was extracted with chloroform (×3)
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated to dryness in vacuo
  6. customThe residue was purified by Biotage (hexane/EtOAc, 0-30%, 40 min)

出典と根拠

ORDレコード
ord-14e99e0d2baf4681bdec4a94c1991339
出典データセット
uspto-grants-2011_10
特許番号
US08030518B2

反応ノート

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