Sodium cyanoborohydride → (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((1-(5-chloropyrimidin-2-yl)cyclopropyl)amino)-1-hydroxyethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate

HRID 513898Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 513898
[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:36])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:35])[CH2:12][CH2:13][C@@:14]3([CH:31]([OH:34])[CH:32]=O)[CH2:26][C:25](=[O:27])[C:24]([CH:28]([CH3:30])[CH3:29])=[C:15]32)[C:6]1([CH3:38])[CH3:37])(=[O:3])[CH3:2].Cl.[Cl:40][C:41]1[CH:42]=[N:43][C:44]([C:47]2([NH2:50])[CH2:49][CH2:48]2)=[N:45][CH:46]=1.C([BH3-])#N.[Na+]>CO.ClCCCl.[Cl-].[Zn+2].[Cl-]>[C:1]([O:4][C@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[C@@H:7]([CH2:8][CH2:9][C@:10]3([CH3:36])[C@@H:19]2[CH2:18][CH2:17][C@H:16]2[C@@:11]3([CH3:35])[CH2:12][CH2:13][C@@:14]3([CH:31]([OH:34])[CH2:32][NH:50][C:47]4([C:44]5[N:43]=[CH:42][C:41]([Cl:40])=[CH:46][N:45]=5)[CH2:48][CH2:49]4)[CH2:26][C:25](=[O:27])[C:24]([CH:28]([CH3:29])[CH3:30])=[C:15]32)[C:6]1([CH3:37])[CH3:38])(=[O:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 5003444Sodium cyanoborohydrideHCID 86690392(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(1-hydroxy-2-oxoethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetateHCID 1317332871-(5-Chloropyrimidin-2-yl)cyclopropan-1-amine hydrochloride

Produkt 1

HCID 86690394(3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((1-(5-chloropyrimidin-2-yl)cyclopropyl)amino)-1-hydroxyethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetateAusbeute 16,04 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

To a solution of (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(1-hydroxy-2-oxoethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate (104) (545 mg, 1.035 mmol) and 1-(5-chloropyrimidin-2-yl)cyclopropanamine, hydrochloride (105) (213 mg, 1.035 mmol) in methanol (5 ml) and 1,2-dichloroethane (5 ml) was added zinc chloride (141 mg, 1.035 mmol). The reaction mixture was stirred at room temperature overnight. and then sodium cyanoborohydride (65.0 mg, 1.035 mmol) was added. The reaction mixture was allowed to stir for 1 h, then silica gel was added to the mixture and the solvents removed in vacuo to give the residue-silica gel powder which was purified on a silica gel column using petroleum ether/EtOAc (5:1 to 3:1) to afford (3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-((1-(5-chloropyrimidin-2-yl)cyclopropyl)amino)-1-hydroxyethyl)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate (105) as a mixture of diastereomers (200 mg, 0.166 mmol, 16.04% yield) as a yellow foam. LC/MS: m/z calculated 679.4. found 680.3 (M+1)+.

Aufarbeitung

  1. stirringto stir for 1 h
  2. additionsilica gel was added to the mixture
  3. customthe solvents removed in vacuo
  4. customto give the residue-silica gel powder which
  5. customwas purified on a silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-09dcad83feb441dfba05544764b8cd0f
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102685B2

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