Sodium Carbonate → N-[2-({(3R)-1-[4-(6-Azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 1173210Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1173210
[N:1]1([C:5]2[N:10]=[CH:9][C:8]([C:11]3([OH:18])[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]3)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[NH:19]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:25]([CH2:27][NH:28][C:29](=[O:40])[C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=2)=[O:26])[CH2:20]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[N:1]1([C:5]2[N:10]=[CH:9][C:8]([C:11]3([OH:18])[CH2:16][CH2:15][CH:14]([N:19]4[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](=[O:26])[CH2:27][NH:28][C:29](=[O:40])[C:30]5[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:39])[F:38])[CH:31]=5)[CH2:20]4)[CH2:13][CH2:12]3)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

Komponenten

6

Edukt 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamideHCID 595560894-(6-Azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexanone

Produkt 1

HCID 59556061N-[2-({(3R)-1-[4-(6-Azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 4-(6-azetidin-1-ylpyridin-3-yl)-4-hydroxycyclohexanone (115 mg, 0.467 mmol) and N-((R)-pyrrolidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide (140.4 mg, 0.445 mmol) in dry CH2Cl2 (19 mL) was added Na(OAc)3BH (198 mg, 0.934 mmol) in one portion under N2 at rt. The reaction mixture was stirred under N2 overnight (16 h) and treated with Na2CO3 (aq), extrated with CH2Cl2×3, dried, filtered and concentrated to give a crude, which was purified by column chromatography (20:80:0.5 MeOH(EtOAc/NH4OH) to provide 60 mg (25%) of desired isomer product (top spot on TLC) as a white solid. MS (M+H+)=546.1. 1H NMR (CD3OD) δ 8.24 (m, 2H), 8.17 (m, 2H), 7.88 (m, 2H), 7.74 (m, 2H), 6.56 (d, 1H), 4.36 (m, 2H), 4.27 (m, 3H), 4.06 (m, 3H), 3.86 (m, 1H), 3.48 (m, 2H), 3.20 (m, 1H), 2.69 (m, 1H), 2.60 (m, 2H), 2.35-2.30 (m, 4H), 2.20-1.97 (m, 4H), 1.73 (m, 2H).

Aufarbeitung

  1. customdried
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customto give a crude, which
  5. customwas purified by column chromatography (20:80:0.5 MeOH(EtOAc/NH4OH)
  6. customto provide 60 mg (25%) of desired isomer product (top spot on TLC) as a white solid

Quellen und Nachweise

ORD-Eintrag
ord-0fd57764538b47769483d633f4548580
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07834021B2

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