5-Bromoimidazo(1,2-a)pyridine → 2-(1-((2-(imidazo[1,2-a]pyridin-5-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1923308Notes

Reaction equation

HRID 1923308 reaction equation
[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.Br[C:42]1[N:47]2[CH:48]=[CH:49][N:50]=[C:46]2[CH:45]=[CH:44][CH:43]=1>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:50]1[CH:49]=[CH:48][N:47]2[C:42]([C:5]3[N:4]=[C:3]4[C:8]([N:9]=[C:10]([CH2:11][N:12]5[CH2:13][CH2:14][CH:15]([C:18]([OH:21])([CH3:19])[CH3:20])[CH2:16][CH2:17]5)[N:2]4[CH3:1])=[C:7]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[N:6]=3)=[CH:43][CH:44]=[CH:45][C:46]=12

Participants

6

Reactant 2

HCID 130372415-Bromoimidazo(1,2-a)pyridineHCID 596055362-(1-((9-Methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Product 1

HCID 596060332-(1-((2-(imidazo[1,2-a]pyridin-5-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-olYield 58%

Reagents, catalysts & solvents 3

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-[1-(9-methyl-6-morpholin-4-yl-2-(tributylstannanyl)-9H-purin-8-ylmethyl)piperidin-4-yl]propan-2-ol (0.2 g, 0.30 mmol), 5-bromoimidazo[1,2-a]pyridine (0.066 g, 0.33 mmol), copper(I) 2-thiophene carboxylate (0.018 g, 0.09 mmol) and Pd(PPh3)4 (0.052 g, 0.045 mmol) in dioxane (5 mL) was subjected to microwave irradiation at 150° C. for 60 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The eluent was concentrated in vacuo and the resultant residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 94:6) followed 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 698 as a yellow powder (0.085 g, 58%). LCMS: RT=4.17 min, [M+H]+ 491.2. 1H NMR (CDCl3, 400 MHz) δ 9.26 (d, J=1.2 Hz, 1 H); 7.96 (dd, J=8.2, 1.2 Hz, 1 H); 7.76-7.73 (m, 2 H); 7.31 (dd, J=8.2, 5.2 Hz, 1 H); 4.38 (t, J=4.6 Hz, 4 H); 3.96 (s, 3 H); 3.89 (t, J=4.6 Hz, 4 H); 3.75 (s, 2 H); 2.96 (d, J=11.0 Hz, 2 H); 2.11 (t, J=11.0 Hz, 2 H); 1.76 (d, J=11.0 Hz, 2 H); 1.44-1.29 (m, 3 H); 1.18 (s, 6 H)

Workup

  1. customirradiation at 150° C. for 60 min
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted
  4. concentrationThe eluent was concentrated in vacuo
  5. customthe resultant residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 94:6)

Sources & evidence

ORD record
ord-50cf4f973497406a814b38e0d0447495
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…