Potassium Acetate → 8-Ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-boronic acid

HRID 387235Notes

Reaction equation

HRID 387235 reaction equation
Br[C:2]1[C:25](=[O:26])[N:24]([CH2:27][CH3:28])[C:5]2[N:6]=[C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:8]=[CH:9][C:4]=2[CH:3]=1.[B:29]1(B2OC(C)(C)C(C)(C)O2)[O:33]C(C)(C)C(C)(C)[O:30]1.C([O-])(=O)C.[K+]>C1(C)C=CC=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:27]([N:24]1[C:5]2[N:6]=[C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:8]=[CH:9][C:4]=2[CH:3]=[C:2]([B:29]([OH:33])[OH:30])[C:25]1=[O:26])[CH3:28]

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 667604546-Bromo-8-ethyl-2-[[4-(4-methylpiperazin-1-yl)phenyl]amino]-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 671196488-Ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-boronic acidYield 18.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Procedure

6-Bromo-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (5, 100 mg, 0.22 mmol), bis(pinacolato)diboron (63 mg, 0.25 mmol), potassium acetate (66 mg, 0.68 mmol) and PdCl2(PPh3)2 (16 mg, 0.02 mmol) were mixed under argon in degassed toluene (3 mL). The resulting suspension was irradiated for 30 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:triethylamine (4:1:0→1:1:0→0:95:5) as eluent. The crude product was dissolved in dichloromethane (10 mL), washed with water (5 mL), and the organic layer was dried over sodium sulfate, filtered and evaporated. The title compound (15 mg, 0.04 mmol, 18%) was obtained as a yellow solid. ESMS m/z 409 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 10.07 (br. s., 1H) 8.85 (s, 1H) 8.52 (s, 2H) 8.28 (s, 1H) 7.64 (br. s., 2H) 6.94 (d, J=9.0 Hz, 2H) 4.33 (q, J=6.9 Hz, 2H) 3.07-3.14 (m, 4H) 2.43-2.47 (m, 4H) 2.22 (s, 3H) 1.26 (t, J=6.9 Hz, 3H).

Workup

  1. customThe resulting suspension was irradiated for 30 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. dissolutionThe crude product was dissolved in dichloromethane (10 mL)
  5. washwashed with water (5 mL)
  6. dry with materialthe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-ffddfbbb79a64c6ab298d17e7be16876
Source dataset
uspto-grants-2013_02
Patent number
US08372970B2

Reaction notes

Loading…