o-Phenetidine → HCID 71549588, compound

HRID 1847980Notes

Reaction equation

HRID 1847980 reaction equation
Br[C:2]1[S:3][C:4]2[CH:10]=[C:9]([CH2:11][N:12]3[C:16]4[CH:17]=[C:18]([O:23][CH3:24])[C:19]([O:21][CH3:22])=[CH:20][C:15]=4[N:14]=[CH:13]3)[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:25]([O:27][C:28]1[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=1[NH2:30])[CH3:26].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH3:22][O:21][C:19]1[C:18]([O:23][CH3:24])=[CH:17][C:16]2[N:12]([CH2:11][C:9]3[CH:8]=[CH:7][C:5]4[N:6]=[C:2]([NH:30][C:29]5[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=5[O:27][CH2:25][CH3:26])[S:3][C:4]=4[CH:10]=3)[CH:13]=[N:14][C:15]=2[CH:20]=1

Participants

5

Reactant 3

HCID 7203o-PhenetidineHCID 81531DiisopropylethylamineHCID 86680991HCID 86680991, compound

Product 1

HCID 71549588HCID 71549588, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 2-bromo-6-((5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazole (60 mg, 0.15 mmol) from Example 2 and 2-ethoxyaniline (61 mg, 0.46 mmol) in anhydrous DMA (600 μL) at rt was added DIEA (155 μL, 0.90 mmol). The mixture was heated in a sealed tube at 110° C. for 72 h. After cooling to rt, the resulting reaction solution was purified by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford 6-((5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)methyl)-N-(2-ethoxyphenyl)benzo[d]thiazol-2-amine (15.2 mg, 22%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.31-8.44 (m, 1H), 8.18 (s, 1H), 7.76 (d, J=1.1 Hz, 1H), 7.51 (d, J=8.1 Hz, 1H), 7.29 (dd, J=1.5, 8.3 Hz, 1H), 7.19 (d, J=2.4 Hz, 2H), 6.91-7.07 (m, 3H), 5.47 (s, 2H), 4.12 (q, J=6.8 Hz, 2H), 3.76 (s, 6H), 1.37 (t, J=7.0 Hz, 3H). LCMS (ESI) m/z 461 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. customthe resulting reaction solution
  3. customwas purified by reverse-phase preparative HPLC
  4. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-dda56578cfe949518c9c79d6c4f98122
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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