Dimethylformamide → 8-ethyl-6-(4-methanesulfonyl-phenyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 1403108Notes

Reaction equation

HRID 1403108 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.[CH3:29][S:30]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)(=[O:32])=[O:31].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN(C)C=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[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]([C:36]2[CH:37]=[CH:38][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:34][CH:35]=2)[C:25]1=[O:26])[CH3:28]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 667604546-Bromo-8-ethyl-2-[[4-(4-methylpiperazin-1-yl)phenyl]amino]-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 679972038-ethyl-6-(4-methanesulfonyl-phenyl)-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-oneYield 15%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

6-Bromo-8-ethyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one (5, 120 mg, 0.27 mmol), 4-methylsulfonylphenylboronic acid (60 mg, 0.30 mmol), K3PO4 (64 mg, 0.30 mmol) and PdCl2(dppf) (25 mg, 0.03 mmol) were mixed under argon in a degassed mixture of dimethylformamide and water (20:1, 4 mL). The resulting suspension was irradiated for 30 min at 140° C. in a microwave reactor. After completion, the reaction mixture was evaporated and the residue purified by ISCO eluting with chloroform:methanol (100:0→98:2). The partially purified product (50 mg) was recrystallized from ethyl acetate. The title compound (21 mg, 0.04 mmol, 15%) was obtained as a yellow solid. ESMS m/z 519 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (s, 1H) 7.99 (d, J=8.3 Hz, 2H) 7.90 (d, J=8.3 Hz, 2H) 7.71 (s, 1H) 7.55 (d, J=8.8 Hz, 2H) 7.30 (br. s, 1H) 6.98 (d, J=8.8 Hz, 2H) 4.51 (q, J=7.0 Hz, 2H) 3.18-3.27 (m, 4H) 3.07 (s, 3H) 2.54-2.67 (m, 4H) 2.37 (s, 3H) 1.39 (t, J=7.0 Hz, 3H).

Workup

  1. customThe resulting suspension was irradiated for 30 min at 140° C. in a microwave reactor
  2. customAfter completion, the reaction mixture was evaporated
  3. customthe residue purified by ISCO
  4. washeluting with chloroform:methanol (100:0→98:2)
  5. customThe partially purified product (50 mg) was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-e8b59c60ebb040be88c4c435734d4737
Source dataset
uspto-grants-2014_12
Patent number
US08912203B2

Reaction notes

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