5-Bromo-N-methoxy-N-methylpyridine-3-carboxamide → (S)-(5-bromopyridin-3-yl)[1-(2-{[tert-butyl(dimethl)silyl]oxy}-1-methylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanone

HRID 1753051Notes

Reaction equation

HRID 1753051 reaction equation
[Si:1]([O:8][CH2:9][CH:10]([N:12]1[C:20]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[C:14](I)=[CH:13]1)[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.[Br:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([CH:39]=1)[C:33](N(OC)C)=[O:34]>C1COCC1>[Br:27][C:28]1[CH:39]=[C:32]([C:33]([C:14]2[C:15]3[CH:16]=[N:17][CH:18]=[CH:19][C:20]=3[N:12]([C@@H:10]([CH3:11])[CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:13]=2)=[O:34])[CH:31]=[N:30][CH:29]=1

Participants

5

Reactant 3

HCID 184722695-Bromo-N-methoxy-N-methylpyridine-3-carboxamideHCID 90093728HCID 90093728, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 131733656(S)-(5-bromopyridin-3-yl)[1-(2-{[tert-butyl(dimethl)silyl]oxy}-1-methylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl]methanoneYield 99.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)-3-iodo-1H-pyrrolo[3,2-c]pyridine (Preparation 55, 16 g, 38.6 mmol) in THF (340 mL) was added iPrMgCl (23.2 mL, 46.3 mmol, 2M solution in THF) dropwise at 0° C. After stirring at this temperature for 1 hour, a solution of 5-bromo-N-methoxy-N-methylnicotinamide (11.4 g, 46.3 mmol) in THF (40 mL) was added slowly to the reaction. The reaction was warmed at room temperature and stirred for 18 hours. The reaction was quenched by the addition of water (200 mL) and the solvents removed in vacuo. The residue was diluted with water (400 mL), extracted into DCM:MeOH (95:5, 200 mL)) five times, the organic layers collected, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a gradient of 10-50% EtOAc in DCM to afford the title compound (18.3 g, 46.5%).

Workup

  1. stirringstirred for 18 hours
  2. customThe reaction was quenched by the addition of water (200 mL)
  3. customthe solvents removed in vacuo
  4. additionThe residue was diluted with water (400 mL)
  5. extractionextracted into DCM:MeOH (95:5, 200 mL)) five times
  6. customthe organic layers collected
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with a gradient of 10-50% EtOAc in DCM

Sources & evidence

ORD record
ord-ba890fa874b0423ab0ec950ff511e547
Source dataset
uspto-grants-2015_10
Patent number
US09163021B2

Reaction notes

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