4-Methylmorpholine → 2-{(4-Fluoro-benzyl)-[2-(7-iodo-1,1-dioxo-1,4-dihydro-1lambda6 benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid ethyl ester

HRID 731364Notes

Reaction equation

HRID 731364 reaction equation
[I:1][C:2]1[CH:17]=[CH:16][C:5]2[NH:6][C:7]([CH2:12][C:13]([OH:15])=O)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.[CH2:18]([O:20][C:21]([CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[NH:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)=[O:22])[CH3:19].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>CN(C)C=O.C(OCC)(=O)C>[CH2:18]([O:20][C:21]([CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[N:29]([CH2:30][C:31]1[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=1)[C:13](=[O:15])[CH2:12][C:7]1[NH:6][C:5]2[CH:16]=[CH:17][C:2]([I:1])=[CH:3][C:4]=2[S:9](=[O:10])(=[O:11])[N:8]=1)=[O:22])[CH3:19]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 576712242-(4-Fluoro-benzylamino)-cyclohexanecarboxylic acid ethyl esterHCID 59853574(7-Iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid

Product 1

HCID 576712042-{(4-Fluoro-benzyl)-[2-(7-iodo-1,1-dioxo-1,4-dihydro-1lambda6 benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

(7-Iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 24b, 2.62 g, 7.16 mmol) was dissolved in anhydrous N,N-dimethylformamide (30 mL). 2-(4-Fluoro-benzylamino)-cyclohexanecarboxylic acid ethyl ester (2.0 g, 7.16 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.44 g, 7.52 mmol). Then N-methylmorpholine (1.52 g, 15.04 mmol) was added into the above reaction mixture. The mixture stirred at 25° C. for 24 h. The solution was diluted with ethyl acetate (200 mL), washed with 1.0 M aqueous hydrochloric acid solution, saturated aqueous sodium bicarbonate solution and saturated aqueous brine solution. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford the crude product, 2-{(4-fluoro-benzyl)-[2-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid ethyl ester, as a yellow oil, which was used directly in the next step without further purification. LC-MS (ESI) calcd for C25H27FIN3O5S 627.07, found 628.3 [M+H+].

Workup

  1. washwashed with 1.0 M aqueous hydrochloric acid solution, saturated aqueous sodium bicarbonate solution and saturated aqueous brine solution
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96e73801e2634ad78840127ccbfbe53c
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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