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

HRID 1662284Notes

Reaction equation

HRID 1662284 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 7929M-XyleneSolvent

Conditions

Temperature
160 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-14e99e0d2baf4681bdec4a94c1991339
Source dataset
uspto-grants-2011_10
Patent number
US08030518B2

Reaction notes

Loading…