1,4-Dioxane → 1-(4-morpholino-6-((3-morpholinoazetidin-1-yl)methyl)thieno[3,2-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-2(3H)-one

HRID 1945758Notes

Reaction equation

HRID 1945758 reaction equation
[N:1]1([C:7]2[C:8]3[S:23][C:22]([CH2:24][N:25]4[CH2:28][CH:27]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:26]4)=[CH:21][C:9]=3[N:10]=[C:11]([NH:13][C:14]3[C:15]([NH2:20])=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[O:35]1CCOC[CH2:36]1>>[O:4]1[CH2:5][CH2:6][N:1]([C:7]2[C:8]3[S:23][C:22]([CH2:24][N:25]4[CH2:28][CH:27]([N:29]5[CH2:30][CH2:31][O:32][CH2:33][CH2:34]5)[CH2:26]4)=[CH:21][C:9]=3[N:10]=[C:11]([N:13]3[C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[NH:20][C:36]3=[O:35])[N:12]=2)[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 312751,4-DioxaneHCID 59606113N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine

Product 1

HCID 596055701-(4-morpholino-6-((3-morpholinoazetidin-1-yl)methyl)thieno[3,2-d]pyrimidin-2-yl)-1H-benzo[d]imidazol-2(3H)-oneYield 32%

Conditions

Temperature
110 °C

Procedure

A mixture of N-[4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thieno[3,2-d]pyrimidin-2-yl]benzene-1,2-diamine (50 mg, 0.10 mmol) and N,N′-carbonyldiimidazole (50 mg, 0.31 mmol) in 1,4-dioxane (0.5 mL) was heated at 110° C. for 4 h. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 98:2 to 96:4) to afford 173 as a tan solid (17 mg, 32%). LCMS (method E): RT=6.42 min, [M+H]+=508.1. 1H NMR (CDCl3, 400 MHz) δ 8.50 (bs, 1 H), 7.76-7.72 (m, 1 H), 7.32 (s, 1 H), 7.13-7.04 (m, 3 H), 4.05 (t, J=4.7 Hz, 4 H), 3.97 (s, 2 H), 3.86 (t, J=4.7 Hz, 4 H), 3.73 (m, 4 H), 3.62 (m, 2 H), 3.06 (s, 3 H), 2.33 (m, 4 H)

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washThe cartridge was then washed with MeOH
  3. washthe desired product was subsequently eluted
  4. customThe product was collected
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM: 2 M NH3 in MeOH 100:0 to 98:2 to 96:4)

Sources & evidence

ORD record
ord-84531799016d4083a2ee0a6febb76fdf
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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