Triethylamine → HCID 10113810, compound

HRID 2218486Notes

Reaction equation

HRID 2218486 reaction equation
[Br:1][C:2]1[C:3]([F:27])=[C:4]([F:26])[C:5]([NH:17][C:18]2[CH:23]=[CH:22][C:21](I)=[CH:20][C:19]=2[F:25])=[C:6]([CH:16]=1)[C:7]([NH:9][O:10][CH2:11][CH:12]([OH:15])[CH2:13][OH:14])=[O:8].C(N(CC)CC)C>O1CCCC1.[Ni]>[Br:1][C:2]1[C:3]([F:27])=[C:4]([F:26])[C:5]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:25])=[C:6]([CH:16]=1)[C:7]([NH:9][O:10][CH2:11][CH:12]([OH:15])[CH2:13][OH:14])=[O:8]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 10231331PD318088

Product 1

HCID 10113810HCID 10113810, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-bromo-N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (0.240 g, 0.429 mmol) and triethylamine (0.2 g, 1.98 mmol) in tetrahydrofuran (16 mL) was hydrogenated over Raney Nickel (0.12 g, pre-rinsed with tetrahydrofuran) at 10 psig at room temperature for a total of 7 hours. The catalyst was removed by filtration and the filtrate was concentrated in vacuo. The afforded residue was partitioned between ethyl acetate and water. The organics were washed twice with water, twice with saturated brine, collected, dried over sodium sulfate, filtered and concentrated in vacuo. HPLC purification was performed using a YMC 30×100 mm 5u (C18) column in 0-100% acetonitrile (3.0% n-propanol)/100-0% water (3.0% n-propanol) at 30 mL/min. The desired fractions were collected, concentrated and dried in a vacuum oven overnight at 50° C. to afford 5-bromo-N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-phenylamino)-benzamide as a white solid (0.054 g, 30%): m.p.=143.5-144.5° C.; 1NMR (400 MHz, DMSO-d6) δ 11.95 (bs, 1H), 8.74 (bs, 1H), 7.68 (d, 1H, J=6.1 Hz), 7.17 (t, 1H, J=9.8 Hz), 7.01-7.04 (m, 1H), 6.94 (m, 2H), 4.81 (m, 1H), 4.57 (m, 1H), 3.86 (m, 1H), 3.69-3.71 (m, 2H), 3.3, (2H, under HDO); MS(APCI+)=435.0/437.0.

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe afforded residue was partitioned between ethyl acetate and water
  4. washThe organics were washed twice with water, twice with saturated brine
  5. customcollected
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customHPLC purification
  10. customThe desired fractions were collected
  11. concentrationconcentrated
  12. customdried in a vacuum oven overnight at 50° C.

Sources & evidence

ORD record
ord-b7783b52d3474f5ab0dcc743d880f094
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

Loading…