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

HRID 2207310Notes

Reaction equation

HRID 2207310 reaction equation
[C:1]([N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2/[C:7](=[CH:14]\[C:15]2[C:20]([CH2:21][O:22]C3CCCCO3)=[CH:19][C:18]([Cl:29])=[CH:17][N:16]=2)/[C:6]1=[O:30])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C(O)C>[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][OH:22])=[CH:19][C:18]([Cl:29])=[CH:17][N:16]=2)[C:6]1=[O:30])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 89821826HCID 89821826, compound

Product 1

HCID 717382771-(tert-butyl)-3-((5-chloro-3-(hydroxymethyl)pyridin-2-yl)methyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-oneYield 90.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 4 (3.0 g, 7.0 mmol) in ethanol (25 mL) was added NaBH4 (0.37 g) in one portion. The resulting suspension was stirred at room temperature for 1 h. The reaction was quenched by adding water (10 mL) followed by 6 N HCl solution in isopropanol (5 mL) slowly. The solution was warmed up to 40° C. and stirred for 3 h. The reaction mixture was mixed with MTBE (50 mL) and saturated aqueous NaCl (50 mL). The organic was separated and washed with water (50 mL). The solution was concentrated under vacuum at 50° C. and residue was triturated with hexane (30 mL). The resulting suspension was stirred at room temperature for 30 min. The precipitates were collected by filtration to give 5 (2.2 g, 86%) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.34 (s, 1H), 8.15 (d, J=4.9 Hz, 1H), 7.74 (s, 1H), 7.30 (d, J=7.1 Hz, 1H), 6.83 (t, J=5.7 Hz, 1H), 4.73 (dd, J=13.4, 4.9 Hz, 1H), 4.63 (dd, J=13.4, 5.7 Hz, 1H), 4.01 (t, J=6.1 Hz, 1H), 3.44 (dd, J=15.4, 5.2 Hz, 1H), 3.17 (dd, J=15.4, 7.2 Hz, 1H), 2.94 (t, J=5.5 Hz, 1H), 1.79 (s, 9H); 13C NMR (CDCl3, 100 MHz): δ 118.72, 159.12, 153.82, 146.45, 145.83 135.72, 135.32, 130.63, 130.27, 124.04, 117.33, 61.40, 58.70, 44.12, 34.01, 28.81.

Workup

  1. customThe reaction was quenched
  2. additionby adding water (10 mL)
  3. temperatureThe solution was warmed up to 40° C.
  4. stirringstirred for 3 h
  5. additionThe reaction mixture was mixed with MTBE (50 mL) and saturated aqueous NaCl (50 mL)
  6. customThe organic was separated
  7. washwashed with water (50 mL)
  8. concentrationThe solution was concentrated under vacuum at 50° C.
  9. customresidue was triturated with hexane (30 mL)
  10. stirringThe resulting suspension was stirred at room temperature for 30 min
  11. filtrationThe precipitates were collected by filtration

Sources & evidence

ORD record
ord-cbb901eb0b2a4f8294fcbab34b978e5d
Source dataset
uspto-grants-2016_06
Patent number
US09376431B2

Reaction notes

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