Hydrochloric Acid → HCID 135410979, compound

HRID 601415Notes

Reaction equation

HRID 601415 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH2:11])[CH:6]=1)[CH3:2].Cl[S:14]([OH:17])(=[O:16])=O.P(Cl)(Cl)(Cl)(Cl)Cl.[NH2:24][C:25]1[CH:53]=[CH:52][C:28]2[NH:29][C:30]([C:35]3[C:36](=[O:51])[N:37]([CH2:46][CH2:47][CH:48]([CH3:50])[CH3:49])[C:38]4[C:43]([C:44]=3[OH:45])=[CH:42][CH:41]=[CH:40][N:39]=4)=[N:31][S:32](=[O:34])(=[O:33])[C:27]=2[CH:26]=1.C(N(CC)CC)C.Cl>ClCCl>[OH:45][C:44]1[C:43]2[C:38](=[N:39][CH:40]=[CH:41][CH:42]=2)[N:37]([CH2:46][CH2:47][CH:48]([CH3:49])[CH3:50])[C:36](=[O:51])[C:35]=1[C:30]1[NH:29][C:28]2[CH:52]=[CH:53][C:25]([NH:24][S:14]([NH:11][C:7]3[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=3)[C:4]([O:3][CH2:1][CH3:2])=[O:12])(=[O:17])=[O:16])=[CH:26][C:27]=2[S:32](=[O:33])(=[O:34])[N:31]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11400Ethyl 3-aminobenzoateHCID 24638Chlorosulfonic acidHCID 24819Phosphorus pentachlorideHCID 1354307103-(7-Amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-1,8-naphthyridin-2(1H)-one

Product 1

HCID 135410979HCID 135410979, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 3-amino-benzoic acid ethyl ester (0.165 g, 1.0 mmol) in dichloromethane (6 mL ) at about 0° C. was added dropwise with chlorosulfonic acid (0.128 g, 1.1 mmol). The reaction mixture was stirred at 25° C. for 1 h and then phosphorous pentachloride (0.229 g, 1.1 mmol) was added and the reaction mixture heated under reflux for 3.5 hours. The reaction mixture was then cooled to about 25° C. and the solvent evaporated under reduced pressure. A solution of the residue in dichloromethane (10 mL) was treated with the product of Example 205 (0.214 g, 0.5 mmol), followed by triethylamine (0.152 g, 1.5 mmol). The reaction mixture was stirred at 25° C. for 3 hours and then poured into 25 mL of 1N aqueous hydrochloric acid. The reaction mixture was then extracted with dichloromethane (3×25 mL). The combined organics were dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with 0-2% methanol/dichloromethane to provide the title compound (0.166 g, 48% yield). 1H NMR (300 MHz, DMSO-d6) δ 0.98 (d, J=6.25 Hz, 6 H) 1.30 (t, J=7.17 Hz, 3 H) 1.56 (m, 2 H) 1.68 (m, 1 H) 4.29 (q, J=6.99 Hz, 2 H) 4.48 (m, 2 H) 7.44 (m, 4 H) 7.57 (d, J=2.21 Hz, 1 H) 7.62 (dt, J=7.36, 1.47 Hz, 1 H) 7.69 (d, J=8.82 Hz, 1 H) 7.74 (s, 1 H) 8.55 (dd, J=8.09, 1.84 Hz, 1 H) 8.88 (dd, J=4.41, 1.84 Hz, 1 H) 10.80 (s, 1 H) 10.88 (s, 1 H) 14.11 (s, 1 H). MS (ESI+) m/z 655.1 (M+H)+, 672.2 (M+NH4)+, 677.0 (M+Na)+, (ESI−) m/z 653.1 (M−H)−.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureunder reflux for 3.5 hours
  3. temperatureThe reaction mixture was then cooled to about 25° C.
  4. customthe solvent evaporated under reduced pressure
  5. stirringThe reaction mixture was stirred at 25° C. for 3 hours
  6. extractionThe reaction mixture was then extracted with dichloromethane (3×25 mL)
  7. dry with materialThe combined organics were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residue was purified by chromatography on silica gel
  11. washeluting with 0-2% methanol/dichloromethane

Sources & evidence

ORD record
ord-e7cf2efde40749209e4df69857d81954
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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