Cesium carbonate → 1-(3-Methoxypyridin-2-yl)-4-(2-phenylthiazol-4-ylmethyl)-[1,4]diazepane

HRID 2063541Notes

Reaction equation

HRID 2063541 reaction equation
Cl[CH2:2][C:3]1[N:4]=[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[S:6][CH:7]=1.Cl.Cl.[CH3:16][O:17][C:18]1[C:19]([N:24]2[CH2:30][CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[N:20][CH:21]=[CH:22][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[CH3:16][O:17][C:18]1[C:19]([N:24]2[CH2:30][CH2:29][CH2:28][N:27]([CH2:2][C:3]3[N:4]=[C:5]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[S:6][CH:7]=3)[CH2:26][CH2:25]2)=[N:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2369694-(Chloromethyl)-2-phenyl-1,3-thiazoleHCID 668934111-(3-Methoxypyridin-2-yl)-[1,4]diazepane dihydrochloride

Product 1

HCID 462050061-(3-Methoxypyridin-2-yl)-4-(2-phenylthiazol-4-ylmethyl)-[1,4]diazepane

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(Chloromethyl)-2-phenyl-1,3-thiazole (52 mg, 0.25 mmol), 1-(3-methoxy-pyridin-2-yl)-[1,4]diazepane dihydrochloride (70 mg, 0.25 mmol), and Cesium carbonate (325 mg, 1.0 mmol) were suspended in anhydrous DMF (1.25 mL). The mixture was stirred at room temperature for 18 hours. The reaction was diluted with EtOAc and washed with H2O (3×25 mL), then brine (25 mL). The organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified on silica (CH2Cl2:MeOH+1% NH4OH) to afford the product. 1H NMR (400 MHz, CDCl3) δ 7.94 (m, 2H), 7.79 (dd, 1H, J=1.6, 4.8 Hz), 7.40 (m, 3H), 7.15 (s, 1H), 6.96 (dd, 1H, J=1.4, 8.2 Hz), 6.66 (dd, 1H, J=4.8, 7.6 Hz), 3.93 (s, 2H), 3.80 (s, 3H), 3.71 (m, 4H), 2.98 (t, 2H, J=5.0 Hz), 2.85 (t, 2H, J=5.6 Hz), 2.04 (quin., 2H, J=5.9 Hz). MS (ES) m/z 381.1 (M+H+).

Workup

  1. washwashed with H2O (3×25 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on silica (CH2Cl2:MeOH+1% NH4OH)
  6. customto afford the product

Sources & evidence

ORD record
ord-30d45a1453394086ac4924714f9b2e70
Source dataset
uspto-grants-2012_10
Patent number
US08288373B2

Reaction notes

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