Tert-butyl 2-ethynyl-6-methoxyphenylcarbamate → Tert-butyl 2-methoxy-6-(3-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)-3-oxoprop-1-ynyl)phenylcarbamate

HRID 1095695Notes

Reaction equation

HRID 1095695 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])#[CH:2].C([Li])CCC.CON(C)[C:27]([C:29]1[N:33]2[CH:34]=[CH:35][C:36]([O:38][CH2:39][CH2:40][O:41][CH3:42])=[CH:37][C:32]2=[N:31][CH:30]=1)=[O:28]>C1COCC1>[CH3:10][O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:1]#[C:2][C:27]([C:29]2[N:33]3[CH:34]=[CH:35][C:36]([O:38][CH2:39][CH2:40][O:41][CH3:42])=[CH:37][C:32]3=[N:31][CH:30]=2)=[O:28])[C:4]=1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 86638604Tert-butyl 2-ethynyl-6-methoxyphenylcarbamateHCID 86638605N-methoxy-7-(2-methoxyethoxy)-N-methylimidazo[1,2-a]pyridine-3-carboxamideHCID 178418339Butyllithium

Product 1

HCID 66781370Tert-butyl 2-methoxy-6-(3-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)-3-oxoprop-1-ynyl)phenylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To tert-butyl 2-ethynyl-6-methoxyphenylcarbamate (1.77 g, 7.18 mmol) in THF (40 mL) was added butyllithium (0.919 g, 14.4 mmol) at −78° C., and the reaction was stirred for 1 hour. N-methoxy-7-(2-methoxyethoxy)-N-methylimidazo[1,2-a]pyridine-3-carboxamide (1.67 g, 5.98 mmol) in THF (55 mL) was then added to the reaction mixture dropwise. After the addition, the cold bath was removed and the reaction was warmed to ambient temperature. Following a 2 hour stir at ambient temperature, the reaction mixture was poured into cold saturated NH4Cl (40 mL) and EtOAc (50 mL). The phases were separated and the aqueous phase was extracted with EtOAc, dried over Na2SO4, filtered and concentrated. The residue was triturated with DCM to give product as a solid. The DCM solution was concentrated and purified by flash column chromatography (EtOAc/MeOH 10:0 to 10:1) to provide the desired product.

Workup

  1. additionAfter the addition
  2. customthe cold bath was removed
  3. waitFollowing a 2 hour
  4. stirringstir at ambient temperature
  5. additionthe reaction mixture was poured into cold saturated NH4Cl (40 mL) and EtOAc (50 mL)
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with EtOAc
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was triturated with DCM
  12. customto give product as a solid
  13. concentrationThe DCM solution was concentrated
  14. custompurified by flash column chromatography (EtOAc/MeOH 10:0 to 10:1)

Sources & evidence

ORD record
ord-e18b4719a2b54b2cb3312e7889dcd2db
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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