4-Methylmorpholine → (1S,2R)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester

HRID 731326Notes

Reaction equation

HRID 731326 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=[O:4].[CH3:20][S:21]([NH:24][C:25]1[CH:40]=[CH:39][C:28]2[NH:29][C:30]([CH2:35][C:36](O)=[O:37])=[N:31][S:32](=[O:34])(=[O:33])[C:27]=2[CH:26]=1)(=[O:23])=[O:22].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>CN(C)C=O>[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C@H:6]1[N:11]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[C:36](=[O:37])[CH2:35][C:30]1[NH:29][C:28]2[CH:39]=[CH:40][C:25]([NH:24][S:21]([CH3:20])(=[O:23])=[O:22])=[CH:26][C:27]=2[S:32](=[O:33])(=[O:34])[N:31]=1)=[O:4]

Participants

6

Reactant 4

HCID 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 57671205(1S,2R)-2-(4-fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester

Product 1

HCID 57671179(1S,2R)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

The crude (1S,2R)-2-(4-fluoro-benzylamino)-cyclohexanecarboxylic acid methyl ester (4.97 mmol) was dissolved in N,N-dimethylformamide (40 mL) at 25° C. and (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 1.47 g, 4.41 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.887, 4.63 mmol), and N-methylmorpholine (1.01 mL, 9.19 mmol) were added sequentially. The reaction mixture was stirred at 25° C. for 2 h, and then was concentrated in vacuo. The residue was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo to afford the crude product, (1S,2R)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester as a yellow oil, which was used directly in the next step without further purification.

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe residue was partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. customdecanted
  5. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-77911c444d44485cb85a7b0569e9726c
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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