Triethylamine → HCID 16221887, compound

HRID 1808945Notes

Reaction equation

HRID 1808945 reaction equation
[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([C:9]([N:11]2[CH2:14][CH:13]([C:15](O)=[O:16])[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:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([C:9]([N:11]2[CH2:14][CH:13]([CH2:15][OH:16])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 4311764Sodium borohydrideHCID 25027257HCID 25027257, compound

Product 1

HCID 16221887HCID 16221887, compoundYield 26.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidine-3-carboxylic acid (196 mg, 0.41 mmol), prepared using procedures similar to those in Example 1, triethylamine (58 μL, 0.41 mmol), PyBOP (213 mg, 0.41 mmol) and sodium borohydride (48 mg, 1.24 mmol) in tetrahydrofuran (2 mL) was stirred at room temperature for 15 hours. The reaction mixture was concentrated in vacuo and the resultant residue was partitioned between 20% aqueous citric acid and ethyl acetate. The organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a colorless residue that was purified by column chromatography. Eluting with 60% ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 48 mg, 0.11 mmol (25%) of [1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-yl]methanol as a white solid. 1H NMR (400 MHz, CDCl3): 7.44 (d, 1H), 7.34 (d, 1H), 7.28-7.23 (m, 1H), 7.04-6.97 (m, 1H), 4.26-4.18 (m, 1H), 4.02-3.94 (m, 2H), 3.78-3.72 (m, 1H), 3.03 (d, 2H), 3.34 (s, 1H), 2.80-2.71 (m, 1H). MS (EI) for C17H14F3IN2O: 463 (MH+).

Workup

  1. customprepared
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resultant residue was partitioned between 20% aqueous citric acid and ethyl acetate
  4. washThe organic portion was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a colorless residue that
  9. customwas purified by column chromatography
  10. washEluting with 60% ethyl acetate in hexanes
  11. customisolated product
  12. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-46d73e3047b645b0927d61f2c79c1bd6
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

Loading…