Boron tribromide → HCID 67160054, compound

HRID 2088510Notes

Reaction equation

HRID 2088510 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:16][C:17]2[C:18]([CH3:26])=[N:19][C:20]([O:24][CH3:25])=[C:21]([CH3:23])[CH:22]=2)[C:5](=[O:15])[N:6]([CH2:8][C@H:9]([CH:12]2[CH2:14][CH2:13]2)[O:10]C)[CH:7]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[N:3]=[C:4]([NH:16][C:17]2[C:18]([CH3:26])=[N:19][C:20]([O:24][CH3:25])=[C:21]([CH3:23])[CH:22]=2)[C:5](=[O:15])[N:6]([CH2:8][C@H:9]([CH:12]2[CH2:14][CH2:13]2)[OH:10])[CH:7]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 131730548HCID 131730548, compound

Product 1

HCID 67160054HCID 67160054, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

A solution of (S)-5-chloro-1-(cyclopropyl-2-methoxyethyl)-3-(6-methoxy-2,5-dimethylpyridin-3-ylamino)pyrazin-2(1H)-one (1.72 g, 4.39 mmol) from Part L in CH2Cl2 (50 mL) at −78° C. was treated with BBr3 (9.65 mL, 9.65 mmol, 1 M in CH2Cl2) dropwise via syringe. After the addition was complete, the reaction mixture was allowed to warm to −40° C., and was stirred at −40 to −35° C. for 45 min. The reaction was quenched by the addition of saturated aqueous NaHCO3. The mixture was then transferred to a separatory funnel containing saturated aqueous NaHCO3 (50 L). The aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography on silica gel (30%→55% ethyl acetate in hexanes) to afford (S)-5-chloro-1-(cyclopropyl-2-hydroxyethyl)-3-(6-methoxy-2,5-dimethylpyridin-3-ylamino)pyrazin-2(1H)-one (1.50 g, 94% yield) as a light yellow amorphous solid: 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.87 (s, 1H), 6.89 (s, 1H), 4.07-4.00 (m, 3H), 3.95 (d, J=6.8 Hz, 1H), 3.94 (s, 3H), 2.42 (s, 3H), 2.17 (s, 3H), 1.27-1.23 (m, 1H), 0.83-0.79 (m, 1H), 0.66-0.62 (m, 1H), 0.55-0.51 (m, 1H), 0.35-0.32 (m, 1H); LRMS (ESI) m/e 365.08 [(M+H)+, calcd for C17H22N4O3Cl 365.14].

Workup

  1. additionAfter the addition
  2. customThe reaction was quenched by the addition of saturated aqueous NaHCO3
  3. customThe mixture was then transferred to a separatory funnel
  4. additioncontaining saturated aqueous NaHCO3 (50 L)
  5. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by column chromatography on silica gel (30%→55% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-cad210b11a6a4f2da68286a2a2bde391
Source dataset
uspto-grants-2013_05
Patent number
US08436000B2

Reaction notes

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