Hydrochloric Acid → 4-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-iodobenzamide

HRID 1849729Notes

Reaction equation

HRID 1849729 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:21]([I:22])=[CH:20][C:16]([C:17]([OH:19])=O)=[C:15]([F:23])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:36]1([S:40]([NH2:43])(=[O:42])=[O:41])[CH2:39][CH2:38][CH2:37]1.N12CCCN=C1CCCCC2.Cl>O1CCCC1.C(OCC)(=O)C>[C:1]12([CH2:11][O:12][C:13]3[C:21]([I:22])=[CH:20][C:16]([C:17]([NH:43][S:40]([N:36]4[CH2:39][CH2:38][CH2:37]4)(=[O:42])=[O:41])=[O:19])=[C:15]([F:23])[CH:14]=3)[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 450805661-AzetidinesulfonamideHCID 867036044-(Adamantan-1-ylmethoxy)-2-fluoro-5-iodobenzoic acid

Product 1

HCID 867036064-(adamantan-1-ylmethoxy)-N-(azetidin-1-ylsulfonyl)-2-fluoro-5-iodobenzamideYield 22%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 4-(adamantan-1-ylmethoxy)-2-fluoro-5-iodobenzoic acid (1.75 g, 4.07 mmol) in anhydrous tetrahydrofuran (20 mL) was added 1,1′-carbonyldiimidazole (1.31 g, 8.10 mmol). The resulting mixture was heated at 70° C. for 30 minutes and then cooled to ambient temperature. Azetidine-1-sulfonamide (1.10 g, 8.10 mmol) was added followed by 1,8-diazabicyclo-[5.4.0]undec-7-ene (1.72 mL, 12.20 mmol) and the reaction mixture was stirred at ambient temperature for 16 hours. After addition of 1 N hydrochloric acid (5 mL) and diluting the mixture with ethyl acetate (150 mL), the organic phase was washed with 1 N hydrochloride acid (5 mL) and brine (10 mL); dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo gave a residue which was purified by silica gel column chromatography using 0-100% ethyl acetate in hexanes as eluent to afford the title compound as an off-white solid (0.48 g, 22%): 11H NMR (300 MHz, CDCl3) δ 8.51 (d, J=8.7 Hz, 1H), 6.56 (d, J=13.7 Hz, 1H), 3.90 (t, J=7.6 Hz, 4H), 3.59 (s, 2H), 2.35-2.15 (m, 2H), 2.12-1.99 (m, 3H), 1.83-1.63 (m, 12H); MS (ES−) m/z 547.1 (M−1).

Workup

  1. temperaturecooled to ambient temperature
  2. washthe organic phase was washed with 1 N hydrochloride acid (5 mL) and brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationFiltration and concentration of the filtrate in vacuo
  5. customgave a residue which
  6. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ecebd837a50a4bb98b0224d51488a133
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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