Triethylamine → Tert-butyl 3-(5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate

HRID 509565Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 509565
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27](O)=[O:28].Cl.[NH2:35][C:36]1([C:47]2[N:52]=[CH:51][CH:50]=[CH:49][N:48]=2)[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.O>[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27]([NH:35][C:36]1([C:47]2[N:48]=[CH:49][CH:50]=[CH:51][N:52]=2)[CH2:37][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39]1)=[O:28]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 592754645-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl) 2-methoxy-4-methylbenzoic acidHCID 89825528Tert-butyl 3-amino-3-(pyrimidin-2-yl)azetidine-1-carboxylate hydrochloride

Produkt 1

HCID 89825398Tert-butyl 3-(5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (50 mg, 0.111 mmol) and tert-butyl 3-amino-3-(pyrimidin-2-yl)azetidine-1-carboxylate hydrochloride (31.8 mg, 0.111 mmol) in DMF (1 ml) in a 25 ml round-bottomed flask was added PyBOP (69.2 mg, 0.133 mmol) and then triethylamine (0.046 ml, 0.332 mmol). The reaction mixture was stirred overnight, and then diluted with water and extracted with EtOAc. The organic layer was further washed with water, dried over sodium sulphate and concentrated. The crude product was then purified by column chromatography (2% methanol in chloroform) to afford tert-butyl 3-(5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzamido)-3-(pyrimidin-2-yl)azetidine-1-carboxylate. Yield: 40 mg (53%). LCMS: (ES+) m/z observed=584.2 (M+H)+ of 4-fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(3-(pyrimidin-2-yl)azetidin-3-ylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe organic layer was further washed with water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customThe crude product was then purified by column chromatography (2% methanol in chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-e5e5305aa1ae4d6fa1e3297750fc136a
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096580B2

Notizen zur Reaktion

Wird geladen…