Diisopropylethylamine → (R)-2-(4-(4-chlorobenzyl)-5-chloro-4H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)chroman-4-yl)pyrrolidine-1-carboxamide

HRID 2063463Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2063463
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:27])([F:26])[C:15]1[CH:24]=[C:23]2[C:18]([C@@H:19]([NH2:25])[CH2:20][CH2:21][O:22]2)=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.Cl.[Cl:38][C:39]1[CH:56]=[CH:55][C:42]([CH2:43][N:44]2[C:48]([C@H:49]3[CH2:53][CH2:52][CH2:51][NH:50]3)=[N:47][N:46]=[C:45]2[Cl:54])=[CH:41][CH:40]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.[Cl-].[Na+].O>[Cl:38][C:39]1[CH:56]=[CH:55][C:42]([CH2:43][N:44]2[C:45]([Cl:54])=[N:46][N:47]=[C:48]2[C@H:49]2[CH2:53][CH2:52][CH2:51][N:50]2[C:2]([NH:25][C@@H:19]2[C:18]3[C:23](=[CH:24][C:15]([C:14]([F:13])([F:26])[F:27])=[CH:16][CH:17]=3)[O:22][CH2:21][CH2:20]2)=[O:4])=[CH:41][CH:40]=1

Komponenten

8

Edukt 5

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 46911908(S)-7-(trifluoromethyl)chroman-4-amineHCID 68811430(R)-4-(4-chlorobenzyl)-3-chloro-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt

Produkt 1

HCID 57650131(R)-2-(4-(4-chlorobenzyl)-5-chloro-4H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)chroman-4-yl)pyrrolidine-1-carboxamideAusbeute 174 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel3×HCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirring solution of triphosgene (14.87 mg, 0.05 mmol) in 8 mL of CH2Cl2 at 0° C. was added dropwise a mixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (32.58 mg, 0.15 mmol) and N,N-diisopropylethylamine (0.07841 mL, 0.45 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0° C. for 30 minutes. Then to the mixture at 0° C. was added a solution of (R)-4-(4-chlorobenzyl)-3-chloro-5-(pyrrolidin-2-yl)-4H-1,2,4-triazole HCl salt (50.05 mg, 0.15 mmol) and N,N-diisopropylethylamine (0.07841 mL, 0.45 mmol) in dichloromethane (2 mL) slowly. The resulting mixture was stirred 0° C. for 30 minutes, then at room temperature overnight. The reaction mixture was treated with sat. aqueous NaHCO3 (10 mL) and brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% of MeOH) afforded the desired product as a brown oil (47 mg, 58.0%).

Aufarbeitung

  1. stirringThe resulting mixture was stirred 0° C. for 30 minutes
  2. customat room temperature
  3. customovernight
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customFlash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% of MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-c31f779cbfe747e7b7132c3d499bed73
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288371B2

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