Water → 2-(5-Fluoro-2-(hydroxymethyl)-3-(8-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)imidazo[1,2-a]pyridin-6-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one

HRID 1024011노트

반응식

HRID 1024011 반응식
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.C([O:28][CH2:29][C:30]1[C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][C:33]([F:45])=[CH:32][C:31]=1[N:46]1[CH2:58][CH2:57][N:49]2[C:50]3[CH2:51][CH2:52][CH2:53][CH2:54][C:55]=3[CH:56]=[C:48]2[C:47]1=[O:59])(=O)C.C([O-])([O-])=O.[Cs+].[Cs+].O>CC#N.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]>[F:45][C:33]1[CH:34]=[C:35]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[CH:14][N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=2)[C:30]([CH2:29][OH:28])=[C:31]([N:46]2[CH2:58][CH2:57][N:49]3[C:50]4[CH2:51][CH2:52][CH2:53][CH2:54][C:55]=4[CH:56]=[C:48]3[C:47]2=[O:59])[CH:32]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 580442052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl AcetateHCID 86684119HCID 86684119, 화합물

생성물 1

HCID 715538632-(5-Fluoro-2-(hydroxymethyl)-3-(8-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)imidazo[1,2-a]pyridin-6-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one수율 28%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6342Acetonitrile용매

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온도
140 °C

실험 절차

A 25 mL sealed tube was charged with 101b (300 mg, 0.88 mmol), 101l (423 mg, 0.88 mmol), Cs2CO3 (572 mg, 1.76 mmol), Pd2(dba)3 (80 mg, 0.09 mmol) suspended in CH3CN (25 mL), and H2O (1 mL). The mixture was heated at 140° C. under microwave irradiation for 1 hour. It was then evaporated and the residue was purified by silica-gel column eluting with 10:1 methylene chloride/methanol to give the crude product, which was further purified by reverse phase Combi-flash eluting with 0.3% NH4HCO3 in 1:4 water/CH3CN to afford 101 as a yellow solid (150 mg, 28%). MS: (M+H)+ 621. 1H NMR (500 MHz, DMSO) δ 8.94 (s, 1H), 8.27 (d, J=1.5, 1H), 8.16 (d, J=1.5, 1H), 7.96 (d, J=1.0, 1H), 7.91 (d, J=2.5, 1H), 7.58 (d, J=1.5, 1H), 7.33-7.42 (m, 3H), 7.25-7.28 (m, 1H), 6.53 (s, 1H), 4.88 (t, J=4.5, 1H), 4.30 (d, J=4.5, 2H), 4.12-4.20 (m, 3H), 3.90-3.92 (m, 1H), 3.06 (t, J=4.5, 4H), 2.53-2.65 (m, 2H), 2.43-2.48 (m, 6H), 2.21 (s, 3H), 1.76-1.81 (m, 2H), 1.67-1.71 (m, 2H)

후처리

  1. customA 25 mL sealed tube
  2. customIt was then evaporated
  3. customthe residue was purified by silica-gel column
  4. washeluting with 10:1 methylene chloride/methanol
  5. customto give the crude product, which
  6. customwas further purified by reverse phase Combi-flash
  7. washeluting with 0.3% NH4HCO3 in 1:4 water/CH3CN

출처 및 근거

ORD 기록
ord-d33ddc357ca24b039217be1dcdfe5a64
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722676B2

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