5-Bromoimidazo(1,2-a)pyridine → HCID 59605843, compound

HRID 1923005Notes

Reaction equation

HRID 1923005 reaction equation
[N:1]1([C:7]2[C:8]3[O:28][C:27]([CH2:29][N:30]4[CH2:33][CH:32]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH2:31]4)=[CH:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[C:41]1[N:46]2[CH:47]=[CH:48][N:49]=[C:45]2[CH:44]=[CH:43][CH:42]=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.C1C=C(C([O-])=O)SC=1.[Cu+]>[N:49]1[CH:48]=[CH:47][N:46]2[C:41]([C:11]3[N:12]=[C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)[C:8]4[O:28][C:27]([CH2:29][N:30]5[CH2:31][CH:32]([N:34]6[CH2:39][CH2:38][O:37][CH2:36][CH2:35]6)[CH2:33]5)=[CH:26][C:9]=4[N:10]=3)=[CH:42][CH:43]=[CH:44][C:45]=12

Participants

6

Reactant 2

HCID 130372415-Bromoimidazo(1,2-a)pyridineHCID 59605624HCID 59605624, compound

Product 1

HCID 59605843HCID 59605843, compoundYield 47.5%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 4-morpholin-4-yl-6-(3-morpholin-4-yl-azetidin-1-ylmethyl)-2-tributylstannanylfuro[3,2-d]pyrimidine (227 mg, 0.35 mmol), 5-bromoimidazo[1,2-a]pyridine (84 mg, 0.43 mmol), tetrakis(triphenylphosphine)palladium (40 mg, 10 mol %) and CuTC (16 mg, 24 mol %) in 1,4-dioxane (4 mL) was purged with argon gas then subjected to microwave irradiation at 140° C. for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g); the cartridge was washed with MeOH/DCM before the desired product was eluted with 2 M NH3 in MeOH/DCM. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:NH3/MeOH (2 M); gradient from 100:0 to 96:4)), 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 afford 250 as a cream foam (79 mg, 47%). LCMS (Method G): RT=3.22 min, M+H+=476. 1H NMR (CDCl3, 400 MHz) δ 9.14 (s, 1 H); 7.87 (dd, J=7.2, 1.2 Hz, 1H); 7.77 (d, J=8.9 Hz, 1 H); 7.74 (d, J=1.2 Hz, 1 H); 7.31 (dd, J=8.9, 7.2 Hz, 1 H); 6.76 (s, 1 H); 4.10 (t, J=4.7 Hz, 4 H); 3.89 (t, J=4.7 Hz, 4 H); 3.84 (s, 2 H); 3.74 (t, J=4.5 Hz, 4 H); 3.62 (t, J=6.2 Hz, 2 H); 3.15-3.02 (m, 3 H) and 2.35 (m, 4 H)

Workup

  1. customwas purged with argon gas
  2. customirradiation at 140° C. for 30 min
  3. washthe cartridge was washed with MeOH/DCM before the desired product
  4. washwas eluted with 2 M NH3 in MeOH/DCM
  5. customThe product was collected
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:NH3/MeOH (2 M); gradient from 100:0 to 96:4)),

Sources & evidence

ORD record
ord-01ec73237aaf47a0b0a8ae68a450bc6b
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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