Water → HCID 118195071, compound

HRID 1048692Notes

Reaction equation

HRID 1048692 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]2[N:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]3=[N:18][C:17]=2[CH2:25][O:26][CH2:27][C:28](Cl)=[O:29])=[CH:10][CH:9]=1.O>ClCCl>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]2[N:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]3=[N:18][C:17]=2[CH2:25][O:26][CH2:27][C:28]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[O:29])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 962WaterHCID 8083MorpholineHCID 118195194HCID 118195194, compound

Product 1

HCID 118195071HCID 118195071, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.806 ml (9.25 mmol) of morpholine were solubilised in 4 ml of dichloromethane with magnetic stirring, a solution of 2-((3-((4-fluorophenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methoxy)acetyl chloride in 4 ml of dichloromethane was added and then the mixture was added at r.t. for 1 h before being treated with 10 ml of water. The aqueous phase was extracted with 2×5 ml of dichloromethane. The combined organic phases were washed with 5 ml of a saturated NaCl aqueous solution, dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by flash chromatography on a silica gel cartridge (eluent: ethyl acetate 100%). 0.211 g (yield=58%) of 2-((3-((4-fluorophenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methoxy)-1-morpholino ethanone were obtained as a pale yellow solid. LC-MS: m/z=394 (MH+); UV purity at 254 nm=99%. 1H NMR (300 MHz, DMSO) δ 8.62 (d, J=6.8 Hz, 1H), 7.74 (dd, J=8.7, 5.5 Hz, 2H), 7.67 (d, J=9.0 Hz, 1H), 7.50-7.39 (m, 1H), 7.33 (t, J=8.9 Hz, 2H), 7.12 (t, J=6.8 Hz, 1H), 4.75 (s, 2H), 4.27 (s, 2H), 3.55-3.46 (m, 4H), 3.39 (s, 4H).

Workup

  1. additionthe mixture was added at r.t. for 1 h
  2. extractionThe aqueous phase was extracted with 2×5 ml of dichloromethane
  3. washThe combined organic phases were washed with 5 ml of a saturated NaCl aqueous solution
  4. customdried on Na2SO4 which
  5. customwas then removed by filtration
  6. concentrationThe obtained filtrate was concentrated in vacuo
  7. customThe crude residue was purified by flash chromatography on a silica gel cartridge (eluent: ethyl acetate 100%)

Sources & evidence

ORD record
ord-4e75e2b0e5f946ebb33e1164de6b7e05
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

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