(Dimethyl sulfide)trihydroboron → 1-[4-(Aminomethyl)benzyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1h)-one

HRID 1867163Notes

Reaction equation

HRID 1867163 reaction equation
[Cl:1][C:2]1[C:3](=[O:29])[N:4]([CH2:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=O)=[CH:22][CH:21]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].CSC.B>O1CCCC1>[NH2:26][CH2:24][C:23]1[CH:27]=[CH:28][C:20]([CH2:19][N:4]2[C:5]([CH3:18])=[CH:6][C:7]([O:8][CH2:9][C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=3[F:17])=[C:2]([Cl:1])[C:3]2=[O:29])=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 12423031(Dimethyl sulfide)trihydroboron3×HCID 22050085HCID 22050085, compound

Product 1

HCID 220509511-[4-(Aminomethyl)benzyl]-3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1h)-oneYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The compound of Example 606 (10.0 g, 23.38 mmol) was suspended in tetrahydrofuran (100 mL) and cooled in an ice-bath. Borane dimethyl sulfide (29.9 mL, 2.0 M in tetrahydrofuran, 59.7 mmol) was added. The resulting mixture was heated to reflux overnight and then cooled in an ice-bath. Additional borane dimethyl sulfide (5.85 mL, 2.0 M in tetrahydrofuran, 11.7 mmol) was added. The resulting mixture was heated to reflux overnight and the cooled to room temperature. The flask was fitted with a distillation head and the reaction was partially concentrated. Additional borane dimethyl sulfide (5.85 mL, 2.0 M in tetrahydrofuran, 11.7 mmol) was added. The mixture was heated to reflux overnight and the cooled in an ice-bath. The reaction was quenched by the addition of 1.0 N HCl (75.0 mL) then partially concentrated. The aqueous layer was made alkaline with 2.5 N NaOH and a precipitate developed. The solid was collected by filtration washing with diethyl ether to give a pale purple solid (3.00 g, 32%). 1H NMR (400 MHz, DMSO-d6) δ 7.64 (app q, J=7.9 Hz, 1H), 7.44 (d, J=7.9 Hz, 2H), 7.32 (app dt, J=2.4, 9.9 Hz, 1H), 7.14 (app dt, J=1.9, 8.5 Hz, 1H), 7.13 (d, J=7.9 Hz, 2H), 6.61 (s, 1H), 5.27 (s, 4H), 3.90 (s, 2H), 2.29 (s, 3H).

Workup

  1. temperaturecooled in an ice-bath
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux overnight
  4. temperaturecooled in an ice-bath
  5. temperatureThe resulting mixture was heated
  6. temperatureto reflux overnight
  7. customThe flask was fitted with a distillation head
  8. concentrationthe reaction was partially concentrated
  9. temperatureThe mixture was heated
  10. temperatureto reflux overnight
  11. temperaturethe cooled in an ice-bath
  12. customThe reaction was quenched by the addition of 1.0 N HCl (75.0 mL)
  13. concentrationthen partially concentrated
  14. filtrationThe solid was collected by filtration
  15. washwashing with diethyl ether

Sources & evidence

ORD record
ord-8e12b730acb44edb973ba211ffa18952
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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