Pyridine → (+/-)-6-{4-[4-(3-Cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfamoyl}chroman-2-carboxylic acid amide

HRID 1071163Notes

Reaction equation

HRID 1071163 reaction equation
N1C=CC=CC=1.[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[C:18](=[O:19])[N:17]([CH2:20][CH2:21][CH2:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[N:16]=[N:15]2)=[CH:10][CH:9]=1.[C:28]([CH:31]1[CH2:40][CH2:39][C:38]2[C:33](=[CH:34][CH:35]=[C:36]([S:41](Cl)(=[O:43])=[O:42])[CH:37]=2)[O:32]1)(=[O:30])[NH2:29]>O1CCCC1>[CH:23]1([CH2:22][CH2:21][CH2:20][N:17]2[C:18](=[O:19])[N:14]([C:11]3[CH:10]=[CH:9][C:8]([NH:7][S:41]([C:36]4[CH:37]=[C:38]5[C:33](=[CH:34][CH:35]=4)[O:32][CH:31]([C:28]([NH2:29])=[O:30])[CH2:40][CH2:39]5)(=[O:42])=[O:43])=[CH:13][CH:12]=3)[N:15]=[N:16]2)[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 155083301-(4-Aminophenyl)4-(3-cyclopentylpropyl)-5-tetrazoloneHCID 22471744(+/-)-2-Carbamoylchroman-6-sulfonyl chloride

Product 1

HCID 20798319(+/-)-6-{4-[4-(3-Cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfamoyl}chroman-2-carboxylic acid amideYield 55.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Pyridine (650 mL, 8.03 mmol) followed by a solution of 1-(4-aminophenyl)4-(3-cyclopentylpropyl)-5-tetrazolone (2.1 g, 7.32 mmol; prepared as described in WO 97/16189) in tetrahydrofuran (50 mL) were added to a cooled (0° C.) solution of the compound from Example 22 (2.02 g, 7.33 mmol) in tetrahydrofuran (50 mL). The mixture was heated to 50° C. overnight. Pyridine (650 mL) was added and the mixture re-heated to 50° C. After 72 hours the mixture was partitioned between ethyl acetate and water. The organic layer was washed with 5% aqueous hydrochloric acid (2×), saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride, dried (MgSO4), and concentrated to a solid (3.7 g). The crude was recrystallized from ethyl acetate (260 mL). The recrystallization mixture was cooled to 0° C. before filtering to give colorless crystals (2.14 g). A second crop afforded 1.09 g. The combined yield was 3.22 g (83%). Mp 202-205° C.; 1H NMR (DMSO-d6, 300 MHz) δ 10.43 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.53 (m, 3H), 7.37 (br s, 1H), 7.26 (d, J=8.8 Hz, 2H), 6.95 (d, J=8.5 Hz, 1H), 4.57 (dd, J=8.5 Hz, 3.3 Hz, 1H), 3.92 (t, J=7.0 Hz, 2H), 2.71 (m, 2H), 2.13 (m, 1H), 1.89 (m, 1H), 1.72 (m, 5H), 1.49 (m, 4H), 1.30 (m, 2H), 1.03 (m, 2H); MS (FAB) m/z 527 (MH+).

Workup

  1. additionwere added to
  2. temperaturethe mixture re-heated to 50° C
  3. customAfter 72 hours the mixture was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with 5% aqueous hydrochloric acid (2×), saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated to a solid (3.7 g)
  7. customThe crude was recrystallized from ethyl acetate (260 mL)
  8. temperatureThe recrystallization mixture was cooled to 0° C.
  9. filtrationbefore filtering

Sources & evidence

ORD record
ord-19adc21019a8467d8bb2d7d69a483f4b
Source dataset
uspto-grants-2005_06
Patent number
US06903218B2

Reaction notes

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