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

Reaction equation

HRID 387236 reaction equation
[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

Participants

6

Reactant 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

Product 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-oneYield 33.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0ac2b40f71444ea392ef75a8fe9be649
Source dataset
uspto-grants-2013_02
Patent number
US08372970B2

Linked notes

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