1,2-Dichloroethane → (S)-tert-Butyl 3-methyl-2-(3-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxamido)butanoate

HRID 2189467Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2189467
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10](=[O:30])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:22]3[N:23]=[CH:24][CH:25]=[C:26]([C:27](O)=[O:28])[C:21]3=[N:20][N:19]=2)=[CH:14][CH:13]=1.Cl.[C:34]([O:38][C:39](=[O:45])[C@H:40]([CH:42]([CH3:44])[CH3:43])[NH2:41])([CH3:37])([CH3:36])[CH3:35].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:43][CH:42]([CH3:44])[C@H:40]([NH:41][C:27]([C:26]1[C:21]2[N:22]([C:18]([C:15]3[CH:14]=[CH:13][C:12]([NH:11][C:10]([NH:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[C:2]([F:31])([F:1])[F:32])=[O:30])=[CH:17][CH:16]=3)=[N:19][N:20]=2)[N:23]=[CH:24][CH:25]=1)=[O:28])[C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:45]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12490702tert-butyl (2S)-2-amino-3-methylbutanoate hydrochlorideHCID 581377793-(4-(3-(2-(Trifluoromethyl)phenyl)ureido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylic acid

Produkt 1

HCID 44256332(S)-tert-Butyl 3-methyl-2-(3-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxamido)butanoateAusbeute 64,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 3-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylic acid (66H) (38 mg, 0.086 mmol) in anhydrous DMF (1 mL) was added L-valine tert-butyl ester hydrochloride (23.4 mg, 0.11 mmol), EDC (24.7 mg, 0.13 mmol), HOBt (17 mg, 0.13 mmol), followed by DIPEA (45 μL, 0.26 mmol). The reaction mixture was stirred at room temperature for 3 h. Analysis by LC/MS indicated the starting material was consumed. The reaction mixture was partitioned between EtOAc and water, then the separated EtOAc layer was washed with water, saturated aqueous NaHCO3, saturated aqueous NaCl, dried (anhydrous Na2SO4), and concentrated. The obtained crude residue was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-100%) in hexanes to afford 33 mg (63%) of the title compound as a yellow solid. HPLC/MS (Method B): retention time=4.04 min, [M+H]+=598.4.

Aufarbeitung

  1. customwas consumed
  2. customThe reaction mixture was partitioned between EtOAc and water
  3. washthe separated EtOAc layer was washed with water, saturated aqueous NaHCO3, saturated aqueous NaCl
  4. dry with materialdried (anhydrous Na2SO4)
  5. concentrationconcentrated
  6. customThe obtained crude residue
  7. customwas purified
  8. washeluting with a gradient of EtOAc (0-100%) in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-618daf6066c849b89a1e9d4555696525
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08324241B2

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