Hydrochloric Acid → (1S,2R,3S,4R)-3-{(2-cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

HRID 548387Notes

Reaction equation

HRID 548387 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@@H:11]([NH:12][CH2:13][CH2:14][CH:15]2[CH2:17][CH2:16]2)[C@H:10]2[CH2:18][C@@H:7]1[CH2:8][CH2:9]2)=[O:5])[CH3:2].[CH3:19][S:20]([NH:23][C:24]1[CH:39]=[CH:38][C:27]2[NH:28][C:29]([CH2:34][C:35](O)=[O:36])=[N:30][S:31](=[O:33])(=[O:32])[C:26]=2[CH:25]=1)(=[O:22])=[O:21].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O>[CH2:1]([O:3][C:4]([C@H:6]1[C@@H:11]([N:12]([CH2:13][CH2:14][CH:15]2[CH2:16][CH2:17]2)[C:35](=[O:36])[CH2:34][C:29]2[NH:28][C:27]3[CH:38]=[CH:39][C:24]([NH:23][S:20]([CH3:19])(=[O:22])=[O:21])=[CH:25][C:26]=3[S:31](=[O:32])(=[O:33])[N:30]=2)[C@H:10]2[CH2:18][C@@H:7]1[CH2:8][CH2:9]2)=[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 66673839(1S,2R,3S,4R)-3-(2-cyclopropyl-ethylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

Product 1

HCID 66674635(1S,2R,3S,4R)-3-{(2-cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of (1S,2R,3S,4R)-3-(2-cyclopropyl-ethylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester (338.2 mg, 1.35 mmol) in anhydrous N,N-dimethylformamide (10 mL) under a nitrogen atmosphere, (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1 g, 493 mg, 1.48 mmol), N-methylmorpholine (0.33 mL, 2.96 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (284 mg, 1.48 mmol) were added sequentially. After shaking at 25° C. for 21 h, additional (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1g, 150 mg, 0.45 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (85 mg, 0.44 mmol) were added. After another 26 h, a 1.0 M aqueous hydrochloric acid solution (12 mL) was added and the mixture was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with saturated aqueous brine solution (15 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude product, (1S,2R,3S,4R)-3-{(2-cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester, as a red oil, which was used in the next step without any further purification. LC-MS (ESI) calcd for C25H34N4O7S2 566.19, found 567.4 [M+H+].

Workup

  1. waitAfter another 26 h
  2. extractionthe mixture was extracted with ethyl acetate (3×60 mL)
  3. washThe combined organic layers were washed with saturated aqueous brine solution (15 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8dff44c61bcc4153a70b20856f1ce1e4
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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