8-(Benzyloxy)-5-bromoimidazo[1,2-a]pyridine → {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

HRID 1946117Notes

Reaction equation

HRID 1946117 reaction equation
[CH3:1][N:2]([CH3:38])[CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[S:18][C:17]3[C:16]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[N:15][C:14]([Sn](CCCC)(CCCC)CCCC)=[N:13][C:12]=3[CH:11]=2)[CH2:5][CH2:4]1.[CH2:39]([O:46][C:47]1[C:48]2[N:49]([CH:54]=[CH:55][N:56]=2)[C:50](Br)=[CH:51][CH:52]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>O1CCOCC1.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.[Cu]I>[CH2:39]([O:46][C:47]1[C:48]2[N:49]([CH:54]=[CH:55][N:56]=2)[C:50]([C:14]2[N:15]=[C:16]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[C:17]3[S:18][C:10]([CH2:9][N:6]4[CH2:5][CH2:4][CH:3]([N:2]([CH3:38])[CH3:1])[CH2:8][CH2:7]4)=[CH:11][C:12]=3[N:13]=2)=[CH:51][CH:52]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 2

HCID 596052618-(Benzyloxy)-5-bromoimidazo[1,2-a]pyridineHCID 59605498Dimethyl-[1-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperidin-4-yl]amine

Product 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}dimethylamineYield 92.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of dimethyl-[1-(4-morpholin-4-yl-2-(tributylstannanyl)thieno[3,2-d]pyrimidin-6-ylmethyl)piperidin-4-yl]amine (230 mg, 0.35 mmol), 8-benzyloxy-5-bromoimidazo[1,2-a]pyridine (127 mg, 0.42 mmol), Pd(PPh3)4 (40 mg, 0.035 mmol) and copper(I) iodide (66 mg, 0.35 mmol) in dioxane (3 mL) was purged with argon gas then heated at 140° C., for 20 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 flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 20:80) to give {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 as a white solid (189 mg, 92%). LCMS (Method H): RT 3.07 min; [M+H]+ 584

Workup

  1. customwas purged with argon gas
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted with 2 M NH3 in MeOH
  4. customevaporated
  5. customThe resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 20:80)

Sources & evidence

ORD record
ord-4375b4db83e94702ac1f1c5b1a4829ea
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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