Hydrochloric Acid → HCID 57671212, compound

HRID 731337Notes

Reaction equation

HRID 731337 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH:11]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:10][CH:9]=[CH:8][CH2:7]1)=[O:5])[CH3:2].[CH3:21][S:22]([NH:25][C:26]1[CH:41]=[CH:40][C:29]2[NH:30][C:31]([CH2:36][C:37](O)=[O:38])=[N:32][S:33](=[O:35])(=[O:34])[C:28]=2[CH:27]=1)(=[O:24])=[O:23].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH:11]([N:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[C:37](=[O:38])[CH2:36][C:31]2[NH:30][C:29]3[CH:40]=[CH:41][C:26]([NH:25][S:22]([CH3:21])(=[O:24])=[O:23])=[CH:27][C:28]=3[S:33](=[O:34])(=[O:35])[N:32]=2)[CH2:10][CH:9]=[CH:8][CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxide2×HCID 57671194HCID 57671194, compound

Product 1

HCID 57671212HCID 57671212, compoundYield 121.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

The crude 6-(4-fluoro-benzylamino)-cyclohex-3-enecarboxylic acid ethyl ester (113.7 mg, 0.41 mmol) was mixed with (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 150 mg, 0.45 mmol) and dissolved in N,N-dimethylformamide (3.4 mL). N-methylmorpholine (100 μL, 0.9 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (86 mg, 0.45 mmol). The reaction mixture was stirred at 25° C. for 16 h. LC-MS analysis indicated that the reaction was incomplete and thus additional (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (30 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (17 mg) were added and the resulted mixture was stirred at 25° C. for 1.5 h. A 1.0 M aqueous hydrochloric acid solution (6.7 mL) was added. The product was extracted with ethyl acetate (3×15 mL) and the combined organic layers were washed with water (10 mL) and saturated aqueous brine solution (15 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo and further dried under high vacuum for 16 h to afford the crude product, 6-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohex-3-enecarboxylic acid ethyl ester (295.4 mg). LC-MS (ESI) calcd for C26H29FN4O7S2 592.15, found 593.4 [M+H+]. This crude product was directly used in next step without further purification.

Workup

  1. stirringthe resulted mixture was stirred at 25° C. for 1.5 h
  2. extractionThe product was extracted with ethyl acetate (3×15 mL)
  3. washthe combined organic layers were washed with water (10 mL) and saturated aqueous brine solution (15 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customfurther dried under high vacuum for 16 h

Sources & evidence

ORD record
ord-9fa2ea8b393f43a98420297c9bd54db7
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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