N-{5-(acetylamino)-2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-2,2-dimethylpropanamide → N-[2-tert-Butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]acetamide

HRID 1435408Notes

Reaction equation

[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([NH:18][CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[C:9]([NH:11][C:12](=O)[C:13]([CH3:16])([CH3:15])[CH3:14])[CH:10]=1)(=[O:3])[CH3:2]>CC(O)=O>[C:13]([C:12]1[N:18]([CH2:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:8]2[CH:7]=[CH:6][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:10][C:9]=2[N:11]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 120 °C

Procedure

N-{5-(acetylamino)-2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-2,2-dimethylpropanamide (33.1 g, 95.3 mmol) was dissolved in AcOH (250 mL). The solution was heated at 120° C. for 8 h. Upon evaporation of the solvent, the residue was dissolved in EtOAc (500 mL), washed with 2N NaOH (3×50 mL), brine (50 mL) and dried over anhydrous Na2SO4. The crude product was recrystallized from EtOAc. Yield: 29.0 g (92%). 1H NMR (400 MHz, CHLOROFORM-D): δ 1.48-1.54 (m, 4 H), 1.56 (s, 9 H), 2.20 (s, 3 H), 2.24-2.35 (m, 1 H), 3.28-3.35 (m, 2 H), 3.96 (t, J=2.83 Hz, 1 H), 3.99 (t, J=3.03 Hz, 1 H), 4.19 (d, J=7.42 Hz, 2H), 7.27 (d, J=8.59 Hz, 1 H), 7.34 (br.s, 1 H), 7.57 (dd, J=8.79, 1.95 Hz, 1 H), 7.67 (d, J=1.95 Hz, 1 H); MS (ESI) (M+H)+=330.04.

Workup

customUpon evaporation of the solvent
dissolutionthe residue was dissolved in EtOAc (500 mL)
washwashed with 2N NaOH (3×50 mL), brine (50 mL)
dry with materialdried over anhydrous Na2SO4
customThe crude product was recrystallized from EtOAc

Sources & evidence

ORD record: ord-aa911cdf35b34a55a5bd5db891ab510e
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615642B2

Reaction notes

Loading…