Dimethylacetamide → HCID 89498721, compound

HRID 1847979Notes

Reaction equation

HRID 1847979 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.CC[N:27](C(C)C)[CH:28]([CH3:30])[CH3:29].[CH3:34][C:35]([N:37]([CH3:39])[CH3:38])=[O:36]>>[C:19]([OH:21])(=[O:36])[CH3:20].[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:27][CH:28]5[CH2:30][CH2:39][N:37]([C:35](=[O:36])[CH3:34])[CH2:38][CH2:29]5)[S:3][C:4]=4[CH:10]=3)[CH:13]=[N:14][C:15]=2[CH:20]=1

Participants

4

Reactant 3

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 86680991HCID 86680991, compound

Product 1

HCID 89498721HCID 89498721, compoundYield 7%

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 2-bromo-6-((5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazole (80 mg, 0.198 mmol) from Example 2,1-(4-aminopiperidin-1-yl)ethanone (56 mg, 0.396 mmol) and DIEA (77 mg, 0.594 mmol) in anhydrous DMA (1 mL) was heated at 120° C. for 15 h. After cooling to rt, the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase to afford 1-(4-((6-((5,6-dimethoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)piperidin-1-yl)ethanone acetate (7 mg, 7%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.15 (s, 1H), 8.08 (d, J=7.2 Hz, 1H), 7.65 (s, 1H), 7.30-7.37 (m, 1H), 7.14-7.25 (m, 3H), 5.41 (s, 2H), 4.18 (m, 1H), 3.94 (m, 1H), 3.75-3.77 (m, 7H), 3.11-3.24 (m, 2H), 2.78-2.85 (m, 1H), 1.95-2.05 (m, 4H), 1.89 (s, 3H), 1.19-1.48 (m, 2H). LCMS (ESI) m/z 466 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. customthe mixture was purified directly by reverse-phase
  3. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase

Sources & evidence

ORD record
ord-d07e1e69361f406787c0342482e18363
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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