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 513898노트

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HRID 513898 반응식
[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]

참가 물질

7

반응물 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

생성물 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 acetate수율 16.04%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 111,2-Dichloroethane용매HCID 887Methanol용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-09dcad83feb441dfba05544764b8cd0f
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102685B2

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