Cesium carbonate → tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 921810노트

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HRID 921810 반응식
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[N:19]1([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:27]2[CH:22]([CH2:23][NH:24][CH2:25][CH2:26]2)[CH2:21][CH2:20]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([O:12][C:11]([NH:10][C:4]1[C:3]([Cl:18])=[C:2]([N:24]2[CH2:25][CH2:26][CH:27]3[N:19]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:20][CH2:21][CH:22]3[CH2:23]2)[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=1)=[O:17])([CH3:16])([CH3:15])[CH3:14]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 49761056(3aR,7aS)-rel-tert-Butyl octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylateHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

생성물 1

HCID 89923255tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate수율 56.6%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
105 °C

실험 절차

A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (440 mg, 1.326 mmol), tert-butyl octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (300 mg, 1.326 mmol), Pd2dba3 (121 mg, 0.133 mmol), BINAP (248 mg, 0.398 mmol), and cesium carbonate (1296 mg, 3.98 mmol) in Dioxane (12 mL) was evacuated and back filled with nitrogen 3× and heated at 105° C. overnight. The reaction mixture was filtered through a plug of celite and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (80 g column, eluting with 5-35% ethyl acetate/hexanes), tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (358 mg) was obtained as a foaming solid.

후처리

  1. customwas evacuated
  2. additionback filled with nitrogen 3×
  3. filtrationThe reaction mixture was filtered through a plug of celite
  4. concentrationthe filtrate was concentrated
  5. customThe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (80 g column, eluting with 5-35% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-827a6eded83a41359efbbd9ed9305cb2
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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