Hydrazine hydrate (1:1) → 12-(5-Chloro-thiophene-2-sulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-diene

HRID 2354871Notes

Reaction equation

HRID 2354871 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]2[CH:15]3[CH2:16][CH2:17][CH2:18][CH:11]2[C:12](=[CH:20]O)[C:13](=O)[CH2:14]3)(=[O:9])=[O:8])=[CH:4][CH:3]=1.O.[NH2:23][NH2:24]>C(O)(=O)C>[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]2[CH:15]3[CH2:16][CH2:17][CH2:18][CH:11]2[C:12]2[CH:20]=[N:23][NH:24][C:13]=2[CH2:14]3)(=[O:9])=[O:8])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 668422859-(5-Chloro-thiophene-2-sulfonyl)-2-hydroxymethylene-9-aza-bicyclo[3.3.1]nonan-3-one

Product 1

HCID 1604547912-(5-Chloro-thiophene-2-sulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-diene

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 9-(5-chloro-thiophene-2-sulfonyl)-2-hydroxymethylene-9-aza-bicyclo[3.3.1]nonan-3-one crude mixture in glacial acetic acid (3 mL) followed by hydrazine monohydrate (1 mL). The reaction mixture was stirred at 100° C. for 1 h after which the solution was cooled to room temperature and quenched by the addition of saturated NaHCO3 solution (until pH>7). The resulting solution was extracted with EtOAc (3×20 mL), the organic extracts were combined, dried (Na2SO4), filtered, concentrated and purified by silica gel column chromatography (Elution with 50% EtOAc/hex, 80% EtOAc/hex, 100% EtOAc, and 5% MeOH/EtOAc) and preparative HPLC to give 12-(5-chloro-thiophene-2-sulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-diene as a white solid. Retention time (min)=1.649 min, Method 1, MS (ESI) 344.0 (M+H); 1H-NMR (300 MHz, CDCl3) δ 7.47 (s, 1H), 7.25 (s, 1H), 7.22 (d, J=4.4 Hz, 1H), 5.28 (b s, 1H), 4.56 (t, J=6.04 Hz, 1H), 3.11 (dd, J=17.58, 7.69 Hz, 1H), 2.66 (d, J=17.58 Hz, 1H), 2.09-1.92 (m, 2H), 1.74-1.57 (m, 3H), 1.44-1.29 (m, 1H); 13C-NMR (75 MHz, CDCl3) δ 143.4, 139.2, 137.7, 131.8, 127.4, 127.0, 117.0, 48.0, 47.9, 32.3, 31.7, 25.4, 15.3 ppm.

Workup

  1. temperaturewas cooled to room temperature
  2. customquenched by the addition of saturated NaHCO3 solution (until pH>7)
  3. extractionThe resulting solution was extracted with EtOAc (3×20 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel column chromatography (Elution with 50% EtOAc/hex, 80% EtOAc/hex, 100% EtOAc, and 5% MeOH/EtOAc) and preparative HPLC

Sources & evidence

ORD record
ord-e8c6d855b2824a3abcfd6e644c2030eb
Source dataset
uspto-grants-2010_07
Patent number
US07754712B2

Reaction notes

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