4-(4-Methylpiperazin-1-yl)aniline → 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester

HRID 1989026Notes

Reaction equation

HRID 1989026 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:25])[C:8]2[CH:13]=[N:12][C:11](S(C)(=O)=O)=[N:10][C:9]=2[N:18]([CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:19]=1)=[O:5])[CH3:2].[CH3:26][N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=2)[CH2:29][CH2:28]1>CC(O)C>[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:25])[C:8]2[CH:13]=[N:12][C:11]([NH:39][C:36]3[CH:35]=[CH:34][C:33]([N:30]4[CH2:29][CH2:28][N:27]([CH3:26])[CH2:32][CH2:31]4)=[CH:38][CH:37]=3)=[N:10][C:9]=2[N:18]([CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:19]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 686792108-Cyclopentyl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester

Product 1

HCID 160594758-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl esterYield 34.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

8-Cyclopentyl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (45 mg, 0.12 mmol) and 4-(4-methyl-piperazin-1-yl)-phenylamine (23 mg, 0.12 mmol) were combined in i-PrOH (1 mL) and heated to 80° C. After 14 h, the solution was concentrated and purified by preparative HPLC (30 mL/min 0-100% H2O/MeCN gradient over 10 min) to provide 19.8 mg of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester. The ester was dissolved in MeOH (2 mL) and cooled to −78° C. in a high pressure vessel. Ammonia was bubbled into the solution for 1 min and the vessel was sealed and allowed to warm to rt. After 14 h, the solution was cooled to −78° C., the vessel was opened and the solution was allowed to warm to rt. The solution was concentrated to provide 5.4 mg of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amide. 1H-NMR (400 MHz, CDCl3:) δ ppm 9.30 (s, 1H), 8.51 (s, 1H), 8.34 (s, 1H), 7.53 (d, 2H, J=8.9 Hz), 6.94 (d, 2H, J=9.0 Hz), 5.23-5.52 (m, 4H), 4.38 (q, 2H, J=7.1 Hz), 3.34-3.36 (m, 4H), 3.00-3.01 (m, 4H), 2.60 (s, 3H), 2.21-2.28 (m, 2H), 1.80-1.93 (m, 6H), 1.40 (t, 3H, J=7.1 Hz). Mass Spectrum (LCMS, ESI pos.) Calcd. For C26H32N6O3: 476.25, found: (M+H) 477.3.

Workup

  1. concentrationthe solution was concentrated
  2. custompurified by preparative HPLC (30 mL/min 0-100% H2O/MeCN gradient over 10 min)

Sources & evidence

ORD record
ord-3e691cc652214c5394b51df9ff51eaff
Source dataset
uspto-grants-2010_01
Patent number
US07642270B2

Reaction notes

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