Dicyclohexylcarbodiimide → (+/-)-(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 2-(phosphonooxy)propanoate

HRID 921709노트

반응식

HRID 921709 반응식
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH2:25][CH3:26])CC3C=CC(OC)=CC=3)[C:12]3=[N:27][CH:28]=[C:29]([C:30]#[N:31])[N:11]3[N:10]=2)=[CH:6][C:5]([C:32]#[N:33])=[CH:4][C:3]=1[N:34]1[CH2:39][CH2:38][C@@H:37]([NH:40][C:41](=[O:44])[O:42][CH3:43])[C@H:36]([OH:45])[CH2:35]1.C([O:53][P:54]([O:64][CH:65]([CH3:69])[C:66](O)=[O:67])([O:56]CC1C=CC=CC=1)=[O:55])C1C=CC=CC=1.C1CCC(N=C=NC2CCCCC2)CC1.ClC1C(NC2N=C(N(CC)CC3C=CC(OC)=CC=3)C3=NC=C(C#N)N3N=2)=CC(C#N)=CC=1N1CC[C@@H](NC(OC)=O)[C@H](C(OP(OCC2C=CC=CC=2)(OCC2C=CC=CC=2)=O)(C)C([O-])=O)C1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[P:54]([O:64][CH:65]([CH3:69])[C:66]([O:45][C@H:36]1[C@H:37]([NH:40][C:41]([O:42][CH3:43])=[O:44])[CH2:38][CH2:39][N:34]([C:3]2[CH:4]=[C:5]([C:32]#[N:33])[CH:6]=[C:7]([NH:8][C:9]3[N:14]=[C:13]([NH:15][CH2:25][CH3:26])[C:12]4=[N:27][CH:28]=[C:29]([C:30]#[N:31])[N:11]4[N:10]=3)[C:2]=2[Cl:1])[CH2:35]1)=[O:67])([OH:56])([OH:55])=[O:53]

참가 물질

7

반응물 4

HCID 10868DicyclohexylcarbodiimideHCID 899186732-((Bis(benzyloxy)phosphoryl)oxy)propanoic acidHCID 131732393methyl((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamateHCID 131732397(3R,4R) 1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4((methoxycarbonyl)amino)piperidin-3-yl-2-((bis(benzyloxy)phosphoryl)oxy)propanoate

생성물 1

HCID 89918705(+/-)-(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 2-(phosphonooxy)propanoate

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (0.040 g, 0.063 mmol), 2-((bis(benzyloxy)phosphoryl)oxy)propanoic acid (0.067 g, 0.19 mmol) in DCM (2 mL) was added DCC (0.039 g, 0.190 mmol) followed DMAP (0.77 mg, 0.006 mmol) and stirred at room temperature for 30 min. After completion of starting material (by LC-MS), reaction mixture was diluted with DCM (50 mL), filtered through celite and filtrate was washed with water and brine solution (5 mL). Combined organic extracts were dried over anhydrous Na2SO4, concentrated and purified by flash chromatography on silica gel using an ISCO system (eluted with 1:1 Hexanes and EtOAc) to give diastereomeric mixture of (3R,4R) 1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4((methoxycarbonyl)amino)piperidin-3-yl-2-((bis(benzyloxy)phosphoryl)oxy)propanoate (0.060 g) as gummy liquid.

후처리

  1. customAfter completion of starting material (by LC-MS), reaction mixture
  2. filtrationfiltered through celite and filtrate
  3. washwas washed with water and brine solution (5 mL)
  4. dry with materialCombined organic extracts were dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. custompurified by flash chromatography on silica gel using
  7. washan ISCO system (eluted with 1:1 Hexanes and EtOAc)
  8. customto give diastereomeric

출처 및 근거

ORD 기록
ord-816d2762bf454ddf9b21448442534c1a
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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