Diisopropylethylamine → Rac-(2r,3r,4r,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid(1-hydroxymethyl-cyclopropylmethyl)-amide

HRID 1806696Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1806696
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)([C:13]#[N:14])[CH:11]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH:10][CH:9]2[C:27](O)=[O:28])[CH:5]=[CH:6][CH:7]=1.[NH2:30][CH2:31][C:32]1([CH2:35][OH:36])[CH2:34][CH2:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[OH:36][CH2:35][C:32]1([CH2:31][NH:30][C:27]([CH:9]2[CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:12]([C:15]3[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=3)([C:13]#[N:14])[CH:11]([CH2:22][C:23]([CH3:25])([CH3:24])[CH3:26])[NH:10]2)=[O:28])[CH2:34][CH2:33]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22379495[1-(Aminomethyl)cyclopropyl]methanolHCID 67296837rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

Produkt 1

HCID 67299214Rac-(2r,3r,4r,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid(1-hydroxymethyl-cyclopropylmethyl)-amideAusbeute 24,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

In a manner similar to the method described in Example 1e, rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (86.2 mg, 0.20 mmol) prepared in Example 1d, (1-aminomethyl-cyclopropyl)-methanol (30.3 mg, 0.3 mmol), HATU (76.0 mg, 0.2 mmol) and iPr2NEt (0.1 mL, 0.55 mmol) in CH2Cl2 (2 mL) was stirred at rt overnight. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, filtered and dried over Na2SO4. The mixture was then concentrated and purified by reverse phase chromatography (20-95% of MeCN/water) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (1-hydroxymethyl-cyclopropylmethyl)-amide (23.9 mg, 24.7%) as a white powder.

Aufarbeitung

  1. washwashed with water, brine
  2. customThe organic phase was separated
  3. filtrationfiltered
  4. dry with materialdried over Na2SO4
  5. concentrationThe mixture was then concentrated
  6. custompurified by reverse phase chromatography (20-95% of MeCN/water)

Quellen und Nachweise

ORD-Eintrag
ord-bd73282ba1e64c2c9aba22684118abfe
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354444B2

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