Hydrochloric Acid → 4-[4'-(1,3-Benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid

HRID 9590

Reaktionsgleichung

Reaktionsgleichung von HRID 9590
NC1C=CC(C2C=CC(C(=O)CC(C)(C)C(OC)=O)=CC=2)=CC=1.ClC1SC2C=CC=CC=2N=1.[S:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[NH:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][C:53]([C:56](=[O:65])[CH2:57][C:58]([CH3:64])([CH3:63])[C:59]([O:61]C)=[O:60])=[CH:52][CH:51]=2)=[CH:46][CH:45]=1.[OH-].[Na+].Cl>C(O)CCC>[S:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[NH:43][C:44]1[CH:45]=[CH:46][C:47]([C:50]2[CH:55]=[CH:54][C:53]([C:56](=[O:65])[CH2:57][C:58]([CH3:63])([CH3:64])[C:59]([OH:61])=[O:60])=[CH:52][CH:51]=2)=[CH:48][CH:49]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 119872-ChlorobenzothiazoleHCID 14798Sodium HydroxideHCID 21985743Methyl 4-(4'-amino-1,1'-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoateHCID 21985746Methyl 4-[4'-(1,3-benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

Produkt 1

HCID 114759304-[4'-(1,3-Benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acidAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 2631-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

In a 8-mL screw-cap vial, a mixture of methyl 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (60 mg, 0.19 mmol) and 2chloro-1,3-benzothiazole (40 mg, 0.23 mmol) in 3 mL n-butanol were heated at 90° C. overnight. The formation of methyl 4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate was monitored by LC-MS. The solvent was removed under reduced pressure. The residue was dissolved in 2 mL tetrahydrofuran/dioxane (1:1), and 3 equivalents of 1 N aqueous sodium hydroxide was added to the solution. The mixture was shaken at rt overnight and then at 50° C. for 2 h. The progress of the hydrolysis reaction was monitored by LC-MS. A solution of 1N aqueous HCl (3.1 equivalents) was then added to the mixture, and the solvent was removed under reduced pressure. The residue was redissolved in 2 mL methanol and a minimum amount of DMF, and the product was isolated and purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to give 40 mg of 4-[4′-(1,3-benzothiazol-2-ylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid (Yield: 45%). 1H NMR (400 MHz, DMSO-d6) δ 11.90 (bs, 1 H), 10.65 (s, 1 H), 8.00 (d, 2 H), 7.90 (d, 2 H), 7.80 (m, 5 H), 7.60 (d, 1 H), 7.35 (t, 1 H), 7.20 (t, 1 H), 3.30 (s, 2 H), 1.10 (s, 6 H); LC-MS m/z 431.2 (MH+), ret. time 3.40 min.

Aufarbeitung

  1. customIn a 8-mL screw-cap vial
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in 2 mL tetrahydrofuran/dioxane (1:1)
  4. waitat 50° C. for 2 h
  5. customThe progress of the hydrolysis reaction
  6. customthe solvent was removed under reduced pressure
  7. dissolutionThe residue was redissolved in 2 mL methanol
  8. customa minimum amount of DMF, and the product was isolated
  9. custompurified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-5a03d33c741245218a6391c02310a4c2
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091228B2

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