Potassium Phosphate, Tribasic → 2-(5-(5-Cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

HRID 1918868노트

반응식

HRID 1918868 반응식
[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1N1CCN2C3CCCCC=3C=C2C1=O)(=[O:3])[CH3:2].Br[C:42]1[CH:43]=[C:44]([NH:50][C:51]2[CH:62]=[C:54]3[CH2:55][N:56]([CH:59]4[CH2:61][CH2:60]4)[CH2:57][CH2:58][N:53]3[N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>CC#N.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:42]1[CH:43]=[C:44]([NH:50][C:51]2[CH:62]=[C:54]3[CH2:55][N:56]([CH:59]4[CH2:61][CH2:60]4)[CH2:57][CH2:58][N:53]3[N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1)(=[O:3])[CH3:2]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 580436915-Bromo-3-(5-cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-oneHCID 670164654-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

생성물 1

HCID 580437822-(5-(5-Cyclopropyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate수율 60.1%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
110 °C

실험 절차

A mixture of 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 210d (105 mg, 0.26 mmol), 135c (100 mg, 0.28 mmol), PdCl2(dppf) (29 mg, 0.039 mmol), K3PO4 (100 mg), and NaOAc (50 mg) in MeCN (10 mL) and water (3 mL) was heated at 110° C. for 2 h. The solvent was evaporated in vacuo. The residue was purified on reverse phase Combi-flash to give 135d (100 mg, 60%). MS: [M+H]+ 640.

후처리

  1. customThe solvent was evaporated in vacuo
  2. customThe residue was purified on reverse phase Combi-flash

출처 및 근거

ORD 기록
ord-a6fbebd3136c4df89490cb988efa2b93
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618107B2

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