Tert-Butylamine → 3-{[(1,1-Dimethylethyl)amino]methyl}-1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)azetidin-3-ol

HRID 605754Notes

Reaction equation

HRID 605754 reaction equation
CC(C1C=C(C(C)C)C=C(C(C)C)C=1S(O[CH2:20][C:21]1([OH:41])[CH2:24][N:23]([C:25]([C:27]2[C:31]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=3[F:40])=[CH:30][S:29][CH:28]=2)=[O:26])[CH2:22]1)(=O)=O)C.[H-].[Na+].[C:44]([NH2:48])([CH3:47])([CH3:46])[CH3:45]>O1CCCC1>[CH3:45][C:44]([NH:48][CH2:20][C:21]1([OH:41])[CH2:24][N:23]([C:25]([C:27]2[C:31]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=3[F:40])=[CH:30][S:29][CH:28]=2)=[O:26])[CH2:22]1)([CH3:47])[CH3:46]

Participants

5

Reactant 3

HCID 6385Tert-ButylamineHCID 24758Sodium hydrideHCID 86621271[1-({4-[(2-Fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)-3-hydroxyazetidin-3-yl]methyl 2,4,6-tris(1-methylethyl)benzenesulfonate

Product 1

HCID 594690283-{[(1,1-Dimethylethyl)amino]methyl}-1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)azetidin-3-olYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

[1-({4-[(2-Fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)-3-hydroxyazetidin-3-yl]methyl 2,4,6-tris(1-methylethyl)benzenesulfonate (101 mg, 0.141 mmol) was dissolved in tetrahydrofuran (2 mL) and was treated with sodium hydride (60 wt % dispersion in oil; 17 mg, 0.425 mmol) at ambient for 20 minutes. Tetrahydrofuran (2 mL) and tert-butylamine (0.1 mL) were added and the mixture was stirred at ambient for 16 h. The mixture was concentrated in vacuo and partitioned between ethyl acetate and water. The organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC and the clean fractions were combined, neutralized with saturated sodium bicarbonate solution and the organic solvent was removed in vacuo. The remaining aqueous residue was extracted twice with ethyl acetate. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford 3-{[(1,1-dimethylethyl)amino]methyl}-1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)azetidin-3-ol (8 mg, 0.016 mmol, 11% yield): 1H NMR (400 MHz, d6-DMSO): 9.64 (br, 1H), 8.08 (d, 1H), 7.59 (dd, 1H), 7.44 (dd, 1H), 7.36 (t, 1H), 7.12 (d, 1H), 4.39 (d, 1H), 4.22 (d, 1H), 4.03 (d, 1H), 3.80 (d, 1H), 2.68 (br, 2H) 1.04 (s, 9H); MS (EI) for C19H23FIN3O2S: 504 (MH+).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompartitioned between ethyl acetate and water
  3. washThe organic portion was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by reverse phase HPLC
  8. customthe organic solvent was removed in vacuo
  9. extractionThe remaining aqueous residue was extracted twice with ethyl acetate
  10. washThe combined organic portion was washed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d29530979f3747b6b597856fa1c1391e
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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