Dimethylformamide → (S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5-(2-(but-3-en-1-yloxy)benzyl)-1,3,4-oxadiazol-2-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

HRID 1481988Notes

Reaction equation

HRID 1481988 reaction equation
[Na+].[CH2:2]([O:5][C:6]1([CH3:35])[CH2:11][CH2:10][N:9]([C:12]2[N:17]3[CH:18]=[C:19]([C:21]([O-:23])=O)[N:20]=[C:16]3[CH:15]=[C:14]([CH3:24])[C:13]=2[C@H:25]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[C:26]([O:28][CH3:29])=[O:27])[CH2:8][CH2:7]1)[CH:3]=[CH2:4].CCN([CH:42]([CH3:44])[CH3:43])C(C)C.CN(C(O[N:53]1[N:61]=N[C:55]2[CH:56]=[CH:57][CH:58]=N[C:54]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:69]([O-:72])(O)=O.[Na+].CC[N+](S(N=C(OC)[O-])(=O)=O)([CH2:79][CH3:80])CC.[CH3:89]N(C=O)C>C(Cl)Cl>[CH2:2]([O:5][C:6]1([CH3:35])[CH2:11][CH2:10][N:9]([C:12]2[N:17]3[CH:18]=[C:19]([C:21]4[O:23][C:54]([CH2:55][C:56]5[CH:57]=[CH:58][CH:80]=[CH:79][C:89]=5[O:72][CH2:69][CH2:44][CH:42]=[CH2:43])=[N:53][N:61]=4)[N:20]=[C:16]3[CH:15]=[C:14]([CH3:24])[C:13]=2[C@H:25]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[C:26]([O:28][CH3:29])=[O:27])[CH2:8][CH2:7]1)[CH:3]=[CH2:4]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117632396(S)-5-(4-(allyloxy)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylic acid sodium salt

Product 1

HCID 118308913(S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5-(2-(but-3-en-1-yloxy)benzyl)-1,3,4-oxadiazol-2-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetateYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (S)-5-(4-(allyloxy)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylic acid sodium salt (76 mg, 0.153 mmol, 1 equiv), 2-(2-(but-3-en-1-yloxy)phenyl)acetohydrazide, HCl (55 mg, 0.214 mmol, 1.4 equiv), DIPEA (0.080 mL, 0.459 mmol, 3 equiv), and HATU (43 mg, 0.113 mmol, 1.4 equiv) in DMF (1.5 mL) was stirred 1 h. The reaction was then added to saturated aqueous NaHCO3 and extracted with DCM (×3). The combined DCM extracts were dried (Na2SO4), and concentrated in vacuo. The crude coupling product was taken up in THF (1.5 mL) and Burgess reagent (146 mg, 0.612 mmol, 4 equiv) was added. The reaction was then heated to 60° C. for 1.5 h. Upon cooling to ambient temperature, the reaction was diluted with DCM and washed with water, saturated aqueous NaHCO3, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (27 mg, 27%) as a yellow film. LCMS (ESI, M+1): 658.35.

Workup

  1. extractionextracted with DCM (×3)
  2. dry with materialThe combined DCM extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. temperatureUpon cooling to ambient temperature
  5. washwashed with water, saturated aqueous NaHCO3
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane)

Sources & evidence

ORD record
ord-2142b6eb8deb49708b955cfef93436b1
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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