Sodium Carbonate → 6-[2,2']bithiophenyl-5-yl-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 387236

반응식

HRID 387236 반응식
[CH2:1]([N:3]1[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=[C:5](B(O)O)[C:4]1=[O:30])[CH3:2].Br[C:32]1[S:36][C:35]([C:37]2[S:38][CH:39]=[CH:40][CH:41]=2)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(COC)OC.O>[S:36]1[C:32]([C:5]2[C:4](=[O:30])[N:3]([CH2:1][CH3:2])[C:8]3[N:9]=[C:10]([NH:13][C:14]4[CH:19]=[CH:18][C:17]([N:20]5[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]5)=[CH:16][CH:15]=4)[N:11]=[CH:12][C:7]=3[CH:6]=2)=[CH:33][CH:34]=[C:35]1[C:37]1[S:38][CH:39]=[CH:40][CH:41]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 6400655-Bromo-[2,2']bithiophenylHCID 671196488-Ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-boronic acid

생성물 1

HCID 671197126-[2,2']bithiophenyl-5-yl-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one수율 33.5%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 18180031Water 1,2-dimethoxyethane용매

실험 절차

8-Ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-boronic acid (21, 71 mg, 0.17 mmol), 5-bromo-2,2′-bithiophene (47 mg, 0.19 mmol), sodium carbonate (55 mg, 0.52 mmol) and Pd(PPh3)4 (20 mg, 0.02 mmol) were mixed under argon in a degassed mixture of dimethoxyethane:water (10:1, 3 mL). The resulting suspension was irradiated for 60 min at 120° C. in a microwave reactor. After completion, the reaction mixture was evaporated and the residue was purified by column chromatography using dichloromethane:methanol (100:5) as eluent. The crude product was triturated with ethyl acetate (10 mL) and collected by filtration. The title compound (30 mg, 0.057 mmol, 33%) was obtained as a yellow solid. ESMS m/z 529 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 9.99 (br. s., 1H) 8.81 (s, 1H) 8.45 (s, 1H) 7.72 (d, J=3.8 Hz, 1H) 7.66 (br. s., 2H) 7.51 (dd, J=5.1, 0.9 Hz, 1H) 7.31-7.37 (m, 2H) 7.11 (dd, J=5.0, 3.8 Hz, 1H) 6.95 (d, J=9.0 Hz, 2H) 4.42 (q, J=7.0 Hz, 2H) 3.04-3.17 (m, 4H) 2.42-2.48 (m, 4H) 2.23 (s, 3H) 1.31 (t, J=7.0 Hz, 3H).

후처리

  1. customThe resulting suspension was irradiated for 60 min at 120° C. in a microwave reactor
  2. customAfter completion, the reaction mixture was evaporated
  3. customthe residue was purified by column chromatography
  4. customThe crude product was triturated with ethyl acetate (10 mL)
  5. filtrationcollected by filtration

출처 및 근거

ORD 기록
ord-0ac2b40f71444ea392ef75a8fe9be649
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372970B2

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