Hydrochloric Acid → (+/-)-2-Aminomethylchroman-6-sulfonic acid {4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenyl}amide

HRID 1004638Notes

Reaction equation

HRID 1004638 reaction equation
B.CSC.[CH:5]1([CH2:10][CH2:11][CH2:12][N:13]2[C:17](=[O:18])[N:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][S:26]([C:29]4[CH:30]=[C:31]5[C:36](=[CH:37][CH:38]=4)[O:35][CH:34]([C:39]([NH2:41])=O)[CH2:33][CH2:32]5)(=[O:28])=[O:27])=[CH:21][CH:20]=3)[N:15]=[N:14]2)[CH2:9][CH2:8][CH2:7][CH2:6]1.Cl.[OH-].[Na+]>O1CCCC1.CO>[CH:5]1([CH2:10][CH2:11][CH2:12][N:13]2[C:17](=[O:18])[N:16]([C:19]3[CH:20]=[CH:21][C:22]([NH:25][S:26]([C:29]4[CH:30]=[C:31]5[C:36](=[CH:37][CH:38]=4)[O:35][CH:34]([CH2:39][NH2:41])[CH2:33][CH2:32]5)(=[O:27])=[O:28])=[CH:23][CH:24]=3)[N:15]=[N:14]2)[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 12423031(Dimethyl sulfide)trihydroboronHCID 20798319(+/-)-6-{4-[4-(3-Cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfamoyl}chroman-2-carboxylic acid amide

Product 1

HCID 15462820(+/-)-2-Aminomethylchroman-6-sulfonic acid {4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenyl}amideYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Borane-methyl sulfide complex (2.0 M solution in tetrahydrofuran, 17.1 mL, 34.2 mmol) was added to a cooled (0° C.) solution of the compound from Example 23 (3.0 g, 5.70 mmol) in tetrahydrofuran (75 mL). The mixture was heated to reflux for 90 minutes then cooled to 0° C. Methanol was added until gas evolution ceased, then 6N HCl (15 mL) was added. The mixture was heated to reflux for 60 minutes then cooled to 0° C. The mixture was brought to pH=12 with 10% aqueous sodium hydroxide and extracted with ethyl acetate (2×). the combined organic layers were dried (Na2SO4) and concentrated to a solid. Silica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 45:45:10 hexane/ethyl acetate/methanol to 90:10 ethyl acetate/methanol) afforded a colorless solid (2.32 g, 80%). Mp 125-130° C. (dec); 1H NMR (DMSO- d6, 300 MHz) δ 7.64 (d, J=8.8 Hz, 2 H), 7.54 (d, J=2.2 Hz, 1 H), 7.47 (dd, J=8.5 Hz, 2.2 Hz, 1 H), 7.22 (d, J=8.8 Hz, 2 H), 6.84 (d, J=8.8 Hz, 1 H), 5.6 (br s, 3 H), 4.04 (m, 1 H), 3.92 (t, J=7.0 Hz, 2 H), 2.83 (d, J=5.5 Hz, 2 H), 2.76 (m, 2 H), 2.0 (m, 1 H), 1.8-1.4 (m, 10 H), 1.30 (m, 2 H), 1.03 (m, 2 H); MS (FAB) m/z 513 (MH+).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 90 minutes
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 60 minutes
  5. temperaturethen cooled to 0° C
  6. extractionextracted with ethyl acetate (2×)
  7. dry with materialthe combined organic layers were dried (Na2SO4)
  8. concentrationconcentrated to a solid
  9. washSilica gel chromatography (gradient elution from 50:50 hexane/ethyl acetate to 45:45:10 hexane/ethyl acetate/methanol to 90:10 ethyl acetate/methanol)

Sources & evidence

ORD record
ord-a7d4d694818f4c17bb9c07a8bfe90e52
Source dataset
uspto-grants-2000_04
Patent number
US06051586

Reaction notes

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