Sodium Chloride → 1-(tert-butyl)-3-((5-chloro-3-(chloromethyl)pyridin-2-yl)methyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one

HRID 2207311Notes

Reaction equation

HRID 2207311 reaction equation
[C:1]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH:7]([CH2:14][C:15]2[C:20]([CH2:21]O)=[CH:19][C:18]([Cl:23])=[CH:17][N:16]=2)[C:6]1=[O:24])([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.S(Cl)([Cl:32])=O.[Na+].[Cl-]>ClCCl>[C:1]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[CH:7]([CH2:14][C:15]2[C:20]([CH2:21][Cl:32])=[CH:19][C:18]([Cl:23])=[CH:17][N:16]=2)[C:6]1=[O:24])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 717382771-(tert-butyl)-3-((5-chloro-3-(hydroxymethyl)pyridin-2-yl)methyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one

Product 1

HCID 717382761-(tert-butyl)-3-((5-chloro-3-(chloromethyl)pyridin-2-yl)methyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-oneYield 94.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5 (5.8 g, 16.8 mmol) in dichloromethane (30 mL) was added DMF (60 μL) and thionyl chloride (2.2 g) at 5° C. The mixture was stirred for 30 min at this temperature followed by addition of 5% aqueous NaCl (30 mL). The organic layer was separated and washed with 5% aqueous NaCl (30 mL). The solvent was removed and the residue was dissolved in heptane (20 mL). The solution was stirred for 10 min and the product was precipitated. The suspension was cooled to 0° C. and filtered to give 6 (5.8 g, 93%) as a solid: 1H NMR (CDCl3, 400 MHz): δ 8.36 (d, J=2.3 Hz, 1H), 8.13 (dd, J=5.1, 1.4 Hz, 1H), 7.65 (d, J=2.3 Hz, 1H), 7.19 (om, 1H), 6.78 (dd, J=7.3, 5.2 Hz, 1H), 4.58 (m, 2H), 4.06 (m, 1H), 3.66 (dd, J=16.3, 4.6 Hz, 1H), 3.32 (dd, J=16.3, 7.5 Hz, 1H), 1.75 (s, 9H); 13C NMR (CDCl3, 100 MHz): δ 178.06, 159.45, 154.58, 147.39, 145.73, 136.87, 132.47, 130.42, 130.11, 123.77, 117.03, 58.51, 43.37, 42.25, 33.69, 28.82.

Workup

  1. customThe organic layer was separated
  2. washwashed with 5% aqueous NaCl (30 mL)
  3. customThe solvent was removed
  4. dissolutionthe residue was dissolved in heptane (20 mL)
  5. stirringThe solution was stirred for 10 min
  6. customthe product was precipitated
  7. filtrationfiltered

Sources & evidence

ORD record
ord-61c1c89f00244d2d9bf859abc96d9236
Source dataset
uspto-grants-2016_06
Patent number
US09376431B2

Reaction notes

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