Phosphorus oxychloride → HCID 58382461, compound

HRID 1628078Notes

Reaction equation

HRID 1628078 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:28]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:23](=O)[N:24]([CH3:26])[CH3:25])[N:20]=[C:15]2[CH:14]=1.O=P(Cl)(Cl)Cl>ClCCCl>[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:28]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:35])([CH3:36])[CH3:34])[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:23]([N:24]([CH3:26])[CH3:25])=[N:22][CH:21]=3)[C:15]=2[CH:14]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58382209HCID 58382209, compound

Product 1

HCID 58382461HCID 58382461, compoundYield 427.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
85 °C

Procedure

A flask was charged with 3-((6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)-1,1-dimethylurea (0.114 g, 0.224 mmol, Preparation #X.1) and DCE (5 mL). A solution of POCl3 (0.063 mL, 0.672 mmol) in DCE (2 mL) was added and mixture was heated to about 85° C. for about 3 h. The mixture was concentrated under reduced pressure and then diluted with EtOAc (15 mL) and washed with saturated aqueous NaCl (10 mL). The organic layer was dried with anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified using silica gel chromatography with an elution gradient of 0 to 100% EtOAc/heptane to give 7-(5-methoxy-1-methyl-1H-indol-3-yl)-N,N-dimethyl-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-amine (0.47 g, 43%): LC/MS (Table 2, Method b) Rt=3.14 min; MS m/z: 491 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additiondiluted with EtOAc (15 mL)
  3. washwashed with saturated aqueous NaCl (10 mL)
  4. dry with materialThe organic layer was dried with anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe material was purified

Sources & evidence

ORD record
ord-e51c4df4a8db46ddb132deb2a1510123
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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