Hydrochloric Acid → N-{3-[(1S,2R,7S,8R)-3-(4-Fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-11-oxa-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

HRID 424207Notes

Reaction equation

HRID 424207 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][C@H:8]2[C@H:13]3[O:14][C@H:10]([CH2:11][CH2:12]3)[C@H:9]2[C:15]([O:17]C)=O)=[CH:4][C:3]=1[CH3:21].[CH3:22][S:23]([NH:26][C:27]1[CH:42]=[CH:41][C:30]2[NH:31][C:32]([CH2:37][C:38](O)=[O:39])=[N:33][S:34](=[O:36])(=[O:35])[C:29]=2[CH:28]=1)(=[O:25])=[O:24].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O>[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:38](=[O:39])[C:37]([C:32]3[NH:31][C:30]4[CH:41]=[CH:42][C:27]([NH:26][S:23]([CH3:22])(=[O:25])=[O:24])=[CH:28][C:29]=4[S:34](=[O:36])(=[O:35])[N:33]=3)=[C:15]([OH:17])[C@H:9]3[C@@H:8]2[C@H:13]2[O:14][C@@H:10]3[CH2:11][CH2:12]2)=[CH:4][C:3]=1[CH3:21]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 66673816methyl (1R,2S,3R,4S)-3-[(4-fluoro-3-methylbenzyl)amino]-7-oxabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 136402451N-{3-[(1S,2R,7S,8R)-3-(4-Fluoro-3-methyl-benzyl)-6-hydroxy-4-oxo-11-oxa-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of methyl (1R,2S,3R,4S)-3-[(4-fluoro-3-methylbenzyl)amino]-7-oxabicyclo[2.2.1]heptane-2-carboxylate (100 mg, 0.34 mmol) and (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1g, 114 mg, 0.34 mmol) in anhydrous N,N-dimethylformamide (4 mL) under a nitrogen atmosphere, N-methylmorpholine (0.075 mL, 0.68 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg, 0.37 mmol) were added sequentially. The mixture was stirred at 25° C. for 2.5 h, poured into 1.0 M aqueous hydrochloric acid solution, and then was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous brine solution, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to afford the amide intermediate which was used in the next step without further purification.

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe combined organic layers were washed with saturated aqueous brine solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-28c2a82dd14a41b7a51a998f27412c8d
Source dataset
uspto-grants-2012_01
Patent number
US08101800B2

Reaction notes

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