Triethylamine → HCID 16223021, compound

HRID 1808975Notes

Reaction equation

HRID 1808975 reaction equation
[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:4]([C:9]([N:11]2[CH2:14][C:13]([C:16]([CH3:21])([CH3:20])[C:17](O)=[O:18])([OH:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[BH4-].[Na+]>O1CCCC1>[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:4]([C:9]([N:11]2[CH2:12][C:13]([C:16]([CH3:21])([CH3:20])[CH2:17][OH:18])([OH:15])[CH2:14]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 4311764Sodium borohydrideHCID 67051644HCID 67051644, compound

Product 1

HCID 16223021HCID 16223021, compoundYield 82.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To solution of 2-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-methylpropanoic acid (300 mg, 0.56 mmol) in tetrahydrofuran (5 mL) was added triethylamine (80 μL, 0.56 mmol), followed by PyBOP (295 mg, 0.56 mmol) and finally sodium borohydride (64 mg, 1.68 mmol). The mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by adding 20% aqueous citric acid, and then partitioned with ethyl acetate. The organic portion was washed with saturated aqueous sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a white solid which was purified by column chromatography. Eluting with 60% ethyl acetate in hexanes, the isolated product was concentrated in vacuo to afford 238 mg, 0.46 mmol (82%) of 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(2-hydroxy-1,1-dimethylethyl)azetidin-3-ol as a white solid. 1H NMR (400 MHz, DMSO): 8.53 (s, 1H), 7.57 (d, 1H), 7.38-7.28 (m, 2H), 7.22-7.15 (m, 1H), 6.70-6.64 (m, 1H), 5.61 (s, 1H), 4.57 (br s, 1H), 4.30-4.27 (m, 1H), 4.18-4.15 (m, 1H), 3.80-3.77 (m, 1H), 3.68-3.64 (m, 1H), 3.25 (s, 2H), 0.76 (d, 6H); MS (EI) for C20H20F3IN2O3: 521 (MH+).

Workup

  1. customThe reaction mixture was quenched
  2. additionby adding 20% aqueous citric acid
  3. custompartitioned with ethyl acetate
  4. washThe organic portion was washed with saturated aqueous sodium bicarbonate, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a white solid which
  9. customwas purified by column chromatography
  10. washEluting with 60% ethyl acetate in hexanes
  11. concentrationthe isolated product was concentrated in vacuo

Sources & evidence

ORD record
ord-147d8300bcf248cbaffe84f9e16547bd
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

Loading…