Cesium carbonate → (trans)-Naphthalen-2-ylmethyl 3-hydroxy-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylate

HRID 1095714Notes

Reaction equation

HRID 1095714 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+].[CH:32]12[O:38][CH:37]1[CH2:36][CH2:35][N:34]([C:39]([O:41][CH2:42][C:43]1[CH:52]=[CH:51][C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH:44]=1)=[O:40])[CH2:33]2.[NH4+].[Cl-]>CC(N(C)C)=O.C(Cl)(Cl)Cl>[OH:38][C@H:32]1[C@H:37]([O:25][C:18]2[CH:19]=[CH:20][CH:21]=[C:22]3[C:17]=2[N:16]=[C:15]([C:12]2[N:9]4[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:7][C:8]4=[N:14][CH:13]=2)[CH:24]=[CH:23]3)[CH2:36][CH2:35][N:34]([C:39]([O:41][CH2:42][C:43]2[CH:52]=[CH:51][C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH:44]=2)=[O:40])[CH2:33]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 66781369HCID 66781369, compoundHCID 86638609Naphthalen-2-ylmethyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate

Product 1

HCID 131729513(trans)-Naphthalen-2-ylmethyl 3-hydroxy-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)piperidine-1-carboxylateYield 58.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (0.10 g, 0.309 mmol) was slurried in DMA (1.0 mL) and treated with Cs2CO3 (0.201 g, 0.618 mmol). After 10 minutes, naphthalen-2-ylmethyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (0.100 g, 0.355 mmol) was added. The reaction was warmed to 90° C. and stirred for 40 hours. The reaction mixture was cooled to ambient temperature then added dropwise into saturated NH4Cl (5 mL). Chloroform (25 mL) was added and the layers were separated. The aqueous layer was washed with CHCl3 and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient from 1 to 20% (6% NH4OH in MeOH)/ethyl acetate to provide the desired product (111 mg). MS ESI (+) m/z 619.2 (M+1) detected.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe layers were separated
  3. washThe aqueous layer was washed with CHCl3
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient from 1 to 20% (6% NH4OH in MeOH)/ethyl acetate

Sources & evidence

ORD record
ord-a183488517674e8ebbf3cc0b4c90bae3
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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