{1-[2-(8-Benzyloxyimidazo[1,2-a]pyridin-5-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperidin-4-yl}dimethylamine → 5-(6-((4-(Dimethylamino)piperidin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)imidazo[1,2-a]pyridin-8-ol

HRID 1946118Notes

Reaction equation

HRID 1946118 reaction equation
C([O:8][C:9]1[C:10]2[N:11]([CH:40]=[CH:41][N:42]=2)[C:12]([C:15]2[N:16]=[C:17]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[C:18]3[S:23][C:22]([CH2:24][N:25]4[CH2:30][CH2:29][CH:28]([N:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]4)=[CH:21][C:19]=3[N:20]=2)=[CH:13][CH:14]=1)C1C=CC=CC=1>C(O)(C(F)(F)F)=O>[CH3:32][N:31]([CH3:33])[CH:28]1[CH2:29][CH2:30][N:25]([CH2:24][C:22]2[S:23][C:18]3[C:17]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)=[N:16][C:15]([C:12]4[N:11]5[CH:40]=[CH:41][N:42]=[C:10]5[C:9]([OH:8])=[CH:14][CH:13]=4)=[N:20][C:19]=3[CH:21]=2)[CH2:26][CH2:27]1

Participants

3

Reactant 1

HCID 59605648{1-[2-(8-Benzyloxyimidazo[1,2-a]pyridin-5-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperidin-4-yl}dimethylamine

Product 1

HCID 1360271385-(6-((4-(Dimethylamino)piperidin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)imidazo[1,2-a]pyridin-8-olYield 10%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of {1-[2-(8-benzyloxyimidazo[1,2-a]pyridin-5-yl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]piperidin-4-yl}dimethylamine (381 mg, 0.65 mmol) in TFA was heated at 140° C., for 10 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH then the desired product was eluted with 2 M NH3 in MeOH. The appropriate fractions were combined and evaporated. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 689 as a yellow solid (32 mg, 10%). LCMS (Method F) RT 3.98 min; [M+H]+ 494. 1H NMR (400 MHz, CH3OH-d4): δ 9.43 (d, J=1.6 Hz, 1 H); 8.04 (d, J=8.2 Hz, 1 H); 7.65 (d, J=1.6 Hz, 1 H); 7.34 (s, 1 H); 6.71 (d, J=8.2 Hz, 1 H); 4.03 (t, J=4.7 Hz, 4 H); 3.87 (m, 7 H); 3.07 (d, J=11.5 Hz, 2 H); 2.37 (s, 6 H); 2.34 (m, 1 H); 2.16 (t, J=11.5 Hz, 2 H); 1.91 (d, J=12.3 Hz, 2 H); 1.66-1.54 (m, 2 H)

Workup

  1. washThe cartridge was washed with MeOH
  2. washthe desired product was eluted with 2 M NH3 in MeOH
  3. customevaporated
  4. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98)

Sources & evidence

ORD record
ord-7834e30dd5e74366902fc1f4c24640de
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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