Sodium Carbonate → 2-[4-((2S)-2-[(Benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoylamino)butoxy]-6-hydroxybenzoic acid

HRID 724690Notes

Reaction equation

HRID 724690 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH:39]2[S:43](=[O:45])(=[O:44])[NH:42][C:41](=[O:46])[CH2:40]2)=[C:35](Br)[CH:34]=1)[C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[C:22]=1[C:23]([O:25]C)=[O:24])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:48]1(B(O)O)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:32][C:33]1[CH:34]=[C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:36]([CH:39]2[S:43](=[O:45])(=[O:44])[NH:42][C:41](=[O:46])[CH2:40]2)=[CH:37][CH:38]=1)[C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[C:22]=1[C:23]([OH:25])=[O:24])=[O:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 58746621Methyl 2-[4-((2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoylamino)butoxy]-6-hydroxybenzoate

Product 1

HCID 587469052-[4-((2S)-2-[(Benzyloxy)carbonyl]amino-3-[6-(1,1-dioxido-3-oxoisothiazolidin-5-yl)biphenyl-3-yl]propanoylamino)butoxy]-6-hydroxybenzoic acidYield 33.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 2-[4-((2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoylamino)butoxy]-6-hydroxybenzoate (12.0 mg, 0.0164 mmol) in toluene (0.4 mL) and 1,4-dioxane (0.4 mL) was added phenylboronic acid (2.40 mg, 0.0196 mmol) and 2 M sodium carbonate in water (0.049 mL). The resulting mixture was degassed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.95 mg, 0.82 μmol) was then added to reaction mixture and heated at 100° C. overnight. The reaction mixture was filtered and purified by preparative LCMS to afford a white solid (3.9 mg, 33%). 1H NMR (400 MHz, CD3OD): δ 7.59 (m, 1H), 7.36 (m, 13H), 6.57 (m, 2H), 5.04 (m, 3H), 4.36 (m, 1H), 4.11 (m, 2H), 3.22 (m, 5H), 2.96 (m, 1H),1.78 (m, 2H), 1.59 (m, 2H). LCMS found for C37H378N3O10S (M+H)+: m/z=716.

Workup

  1. customThe resulting mixture was degassed with nitrogen
  2. filtrationThe reaction mixture was filtered
  3. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-a1ad654a78ca43bda7b16df224afd3a8
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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