Diisopropylethylamine → HCID 58746598, compound

HRID 724693Notes

Reaction equation

HRID 724693 reaction equation
[NH2:1][C@@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[S:33](=[O:35])(=[O:34])[NH:32][C:31](=[O:36])[CH2:30]2)=[C:25]([Br:37])[CH:24]=1)[C:3]([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[C:12]=1[C:13]([O:15][CH3:16])=[O:14])=[O:4].C(N(CC)C(C)C)(C)C.[N:47]1([C:53](Cl)=[O:54])[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1>C(Cl)Cl.CN(C)C=O>[Br:37][C:25]1[CH:24]=[C:23]([CH2:22][C@H:2]([NH:1][C:53]([N:47]2[CH2:52][CH2:51][O:50][CH2:49][CH2:48]2)=[O:54])[C:3]([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[C:12]=2[C:13]([O:15][CH3:16])=[O:14])=[O:4])[CH:28]=[CH:27][C:26]=1[CH:29]1[S:33](=[O:34])(=[O:35])[NH:32][C:31](=[O:36])[CH2:30]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 848104-Morpholinecarbonyl chlorideHCID 58746716HCID 58746716, compound

Product 1

HCID 58746598HCID 58746598, compoundYield 84.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 2-[4-((2S)-2-amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoylamino)butoxy]-6-hydroxybenzoate (30.0 mg, 0.0501 mmol) in methylene chloride (0.4 mL) and N,N-dimethylformamide (0.10 mL) was added N,N-diisopropylethylamine (26.4 μL, 0.152 mmol) and morpholine-4-carbonyl chloride (6.48 μL, 0.0556 mmol) at room temperature. The resulting solution was stirred for 2 h. The reaction was quenched with 1 N HCl solution and diluted with ethyl acetate. The aqueous layer was extracted with ethyl acetate twice. The combined organic solutions were dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by preparative LCMS to afford a white solid (30 mg, 80%). 1H NMR (400 MHz, CD3OD): δ 7.61 (dd, J=9.6, 1.8 Hz, 1H), 7.47 (dd, J=11.3, 8.0 Hz, 1H), 7.35 (m, 1H), 7.24 (t, J=8.3 Hz, 1H), 6.48 (m, 2H), 5.36 (m, 1H), 4.44 (dd, J=8.8, 6.6 Hz, 1H), 3.98 (t, J=5.8 Hz, 2H), 3.87 (s, 3H), 3.59 (m, 4H), 3.43 (dd, J=17.6, 8.4 Hz, 1H), 3.23 (m, 1H), 3.16 (m, 3H), 2.96 (m, 1H), 1.64 (m, 4H). LCMS found for C29H36BrN4O10S (M+H)+: m/z=711, 713.

Workup

  1. customThe reaction was quenched with 1 N HCl solution
  2. additiondiluted with ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate twice
  4. dry with materialThe combined organic solutions were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative LCMS

Sources & evidence

ORD record
ord-303f90c403294944b2b399a453addeee
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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