Acetic Acid → (2S,4R)-1-[3-(5-Bromo-3-fluoro-pyridin-2-yl)-1-methyl-azetidine-3-carbonyl]-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide

HRID 69529Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69529
[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:13][C@@H:12]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])(=[O:16])=[O:15])[CH2:11][N:10]2[C:24]([C:26]2([C:30]3[C:35]([F:36])=[CH:34][C:33]([Br:37])=[CH:32][N:31]=3)[CH2:29][NH:28][CH2:27]2)=[O:25])=[O:8])[CH2:5][CH2:4]1)#[N:2].[C:38]([O-])(=O)C.[Na+].C(O)(=O)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:13][C@@H:12]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])(=[O:15])=[O:16])[CH2:11][N:10]2[C:24]([C:26]2([C:30]3[C:35]([F:36])=[CH:34][C:33]([Br:37])=[CH:32][N:31]=3)[CH2:29][N:28]([CH3:38])[CH2:27]2)=[O:25])=[O:8])[CH2:4][CH2:5]1)#[N:2]

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 71679559(2S,4R)-1-[3-(5-Bromo-3-fluoro-pyridin-2-yl)-azetidine-3-carbonyl]-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide

Produkt 1

HCID 71679560(2S,4R)-1-[3-(5-Bromo-3-fluoro-pyridin-2-yl)-1-methyl-azetidine-3-carbonyl]-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amideAusbeute 40,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a mixture of example 13 (0.05 g, 81.8 μmol, Eq: 1.00), sodium acetate (14.8 mg, 180 μmol, Eq: 2.2) and acetic acid (10.8 mg, 10.3 μl, 180 μmol, Eq: 2.2) in dichloromethane (0.5 ml) was added at 25° C. aqueous formaldehyde solution (36%; 19.1 mg, 17.5 μl, 229 μmol, Eq: 2.8). The mixture was stirred for 45 min, then sodium triacetoxyborohydride (55.5 mg, 262 μmol, Eq: 3.2) was added in one portion at 0-5° C. The cooling bath was removed after 10 min and stirring was continued at 25° C. for further 18 h. The reaction mixture was quenched with aqueous 0.5 M NaOH-solution (2 ml), stirred for 2 min, then the layers were separated. The aqueous layer was extracted with three portions of AcOEt (each 5 ml). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by preparative HPLC to yield the title compound as a colorless amorphous solid (0.0206 g; 40%). m/z=626.1 [M+H]+.

Aufarbeitung

  1. customThe cooling bath was removed after 10 min
  2. stirringstirring
  3. waitwas continued at 25° C. for further 18 h
  4. customThe reaction mixture was quenched with aqueous 0.5 M NaOH-solution (2 ml)
  5. stirringstirred for 2 min
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with three portions of AcOEt (each 5 ml)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-428e008081b942ec8ef1121f46cbb07f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822505B2

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