Water → Tert-butyl 2-((2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)methyl)morpholine-4-carboxylate

HRID 1095682Notes

Reaction equation

HRID 1095682 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[C:18]([OH:25])[CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:37][CH:38]1[O:43][CH2:42][CH2:41][N:40]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:39]1)(=O)=O.O>CC(N(C)C)=O>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[C:18]([O:25][CH2:37][CH:38]5[O:43][CH2:42][CH2:41][N:40]([C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])[CH2:39]5)[CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 57791474Tert-butyl 2-(((methylsulfonyl)oxy)methyl)morpholine-4-carboxylateHCID 66781369HCID 66781369, compound

Product 1

HCID 66781542Tert-butyl 2-((2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)methyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol [prepared as in Example 3, Step C; 50 mg, 0.15 mmol] in anhydrous DMA (2 mL) was added cesium carbonate (150 mg, 0.45 mmol) followed by tert-butyl 2-((methylsulfonyloxy)methyl)morpholine-4-carboxylate (130 mg, 0.45 mmol). The heterogeneous mixture was stirred at 100° C. for 16 hours and allowed to cool. The mixture was treated with water (20 mL) and extracted with EtOAc. The combined organic phases were washed with water and brine, then dried over Na2SO4, filtered and concentrated. The residue was purified via flash column chromatography using gradient elution (CH2Cl2 to 1% MeOH/CH2Cl2 to 2% MeOH/CH2Cl2) to afford tert-butyl 2-((2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)methyl)morpholine-4-carboxylate as a gum. This was dissolved in CH2Cl2 (4 mL) and treated with TFA (1 mL). After stirring for 2 hours at ambient temperature the mixture was concentrated. The residue was triturated with ether, filtered and dried in vacuo to provide 29.1 mg (76%) of desired product as its di-TFA salt as a powder. MS ESI (+) m/z 435.3 (M+1) detected.

Workup

  1. temperatureto cool
  2. extractionextracted with EtOAc
  3. washThe combined organic phases were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via flash column chromatography
  8. washelution (CH2Cl2 to 1% MeOH/CH2Cl2 to 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ad2c3a9ecad24a1792d68d3d3d5e21c8
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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