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Triphenylphosphine → 1-(2-Chloro-3,6-difluorobenzyl)-7-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one

HRID 659599
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인쇄 미리보기

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HRID 659599 반응식
Br[C:2]1[CH:22]=[N:21][C:5]2[NH:6][C:7](=[O:20])[CH2:8][N:9]([CH2:10][C:11]3[C:16]([F:17])=[CH:15][CH:14]=[C:13]([F:18])[C:12]=3[Cl:19])[C:4]=2[CH:3]=1.[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][N:31]=2)[CH2:26][CH2:25]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:19][C:12]1[C:13]([F:18])=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[CH2:10][N:9]1[CH2:8][C:7](=[O:20])[NH:6][C:5]2[N:21]=[CH:22][C:2]([C:33]3[CH:32]=[N:31][C:30]([N:27]4[CH2:26][CH2:25][N:24]([CH3:23])[CH2:29][CH2:28]4)=[CH:35][CH:34]=3)=[CH:3][C:4]1=2
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참가 물질

6

반응물 3

HCID 11776TriphenylphosphineHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 578858627-Bromo-1-(2-chloro-3,6-difluorobenzyl)-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one

생성물 1

HCID 578860121-(2-Chloro-3,6-difluorobenzyl)-7-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one수율 29%

시약·촉매·용매 2

HCID 167845
palladium(II) acetate
촉매
HCID 10311-Propanol용매

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온도
130 °C

실험 절차

A mixture of 7-bromo-1-(2-chloro-3,6-difluorobenzyl)-1,4-dihydro-2H-pyrido[2,3-b]pyrazin-3-one (42 mg, 0.11 mmol), 1-methyl-4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (40 mg, 0.13 mmol), palladium (II) acetate (4 mg) and triphenylphosphine (14 mg) in n-propanol (1.0 mL) was degassed with argon while adding a 1.26 M aqueous solution of Na2CO3 (0.12 mL) followed by water (0.38 mL). This mixture was heated in a microwave for 10 minutes at 130° C., cooled to room temperature and extracted into CH2Cl2. The organic phase was passed through a plug of Na2SO4, absorbed onto florisil and evaporated to dryness. This material was purified by silica gel chromatography by eluting with increasing amounts of 5% NH4OH/methanol in dichloromethane. The isolated material was recrystallized from methanol to give the title compound (15.4 mg, 29%). m.p. 235-236° C. (dec); LCMS: m/z=485/487 (M+H+); 1H-NMR (CDCl3-d6, 400 MHz) δ 8.22 (d, J=2.4 Hz, 1H), 7.89 (d, J=2.4 Hz, 1H), 7.49-7.46 (m, 1H), 7.16 (s, 1H), 7.15-7.06 (m, 1H), 7.05-6.93 (m, 1H), 6.69 (d, J=8.8, 1H), 5.43, (s, 2H), 4.81 (s, 1H), 4.24 (s, 2H), 3.61-3.59 (m, 4H), 2.55-2.52 (m, 4H), 2.36 (s, 3H).

후처리

  1. customwas degassed with argon
  2. additionwhile adding a 1.26 M aqueous solution of Na2CO3 (0.12 mL)
  3. temperaturecooled to room temperature
  4. extractionextracted into CH2Cl2
  5. customabsorbed onto florisil
  6. customevaporated to dryness
  7. customThis material was purified by silica gel chromatography
  8. washby eluting with increasing amounts of 5% NH4OH/methanol in dichloromethane
  9. customThe isolated material was recrystallized from methanol

출처 및 근거

ORD 기록
ord-55803e26100f471d96802a57101125a3
출처 데이터셋
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08080561B2

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