Gamma-Butyrolactone → HCID 58382148, compound

HRID 1628010Notes

Reaction equation

HRID 1628010 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=1.[O:32]1[CH2:36][CH2:35][CH2:34][C:33]1=[O:37].N1C=NC=N1.C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[OH:37][CH2:33][CH2:34][CH2:35][C:36]([NH:22][CH2:21][C:19]1[N:20]=[C:15]2[CH:14]=[C:13]([C:6]3[C:5]4[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=4)[N:8]([CH3:12])[CH:7]=3)[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:16]2=[N:17][CH:18]=1)=[O:32]

Participants

6

Reactant 4

HCID 7302Gamma-ButyrolactoneHCID 92571H-1,2,4-TriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58009787HCID 58009787, compound

Product 1

HCID 58382148HCID 58382148, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A flask was charged with (6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine (0.300 g, 0.686 mmol, Preparation #I.1), dihydrofuran-2(3H)-one (0.063 mL, 0.823 mmol), 1,2,4-triazole (0.009 g, 0.13 mmol), DBU (0.021 mL, 0.13 mmol) and DCM (10 mL). The mixture was heated to about 60° C. and stirred overnight. The mixture was concentrated under reduced pressure and the residue was diluted with EtOAc (10 mL) and washed with water (10 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified by silica gel chromatography with an elution gradient of 0 to 100% EtOAc/heptane to give 4-hydroxy-N-((6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)butanamide (0.150 g, 42%): LC/MS (Table 2, Method b) Rt=2.40 min; MS m/z 524 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with EtOAc (10 mL)
  3. washwashed with water (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe material was purified by silica gel chromatography with an elution gradient of 0 to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-184758e4f61641e0a84465ccdf305530
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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