1-Methylpiperazine → 2-[2-Hydroxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amide

HRID 1989030Notes

Reaction equation

HRID 1989030 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[OH:15].FC1C=CC([N+]([O-])=O)=CC=1O.CN1CCNCC1.[CH2:34]1[C:42]2[C:37](=[CH:38][C:39]([N:43]3[C:48]4[N:49]=[C:50](S(C)(=O)=O)[N:51]=[CH:52][C:47]=4[C:46](=[O:57])[C:45]([C:58]([NH2:60])=[O:59])=[CH:44]3)=[CH:40][CH:41]=2)[CH2:36][CH2:35]1>>[OH:15][C:3]1[CH:4]=[C:5]([N:8]2[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]2)[CH:6]=[CH:7][C:2]=1[NH:1][C:50]1[N:51]=[CH:52][C:47]2[C:46](=[O:57])[C:45]([C:58]([NH2:60])=[O:59])=[CH:44][N:43]([C:39]3[CH:38]=[C:37]4[C:42](=[CH:41][CH:40]=3)[CH2:34][CH2:35][CH2:36]4)[C:48]=2[N:49]=1

Participants

5

Reactant 4

HCID 531671-MethylpiperazineHCID 234981002-Fluoro-5-nitrophenolHCID 686788178-Indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amideHCID 686788702-Amino-5-(4-methylpiperazin-1-yl)phenol

Product 1

HCID 160595332-[2-Hydroxy-4-(4-methyl-piperazin-1-yl)-phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amideYield 40%

Procedure

Using the procedure outlined in Example 23 (c), the title compound was prepared from 2-amino-5-(4-methyl-piperazin-1-yl)-phenol (5 mg, prepared using the procedure outlined in Example 1 (F) from 1-fluoro-2-hydroxy-4-nitrobenzene and 1-methyl-piperazine) and 8-indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amide (from Example 23 (b), 7 mg). Purification by preparative HPLC (32 mL/min, 5-100% H2O/MeCN (0.01% TFA, v/v) gradient over 10 min) followed by a basic aqueous work-up gave the title compound as a yellow solid (3.7 mg, 40%). 1H NMR (400 MHz, CD3OD) δ (ppm): 9.25 (br, 1H), 8.73 (s, 1H), 7.44 (d, J=8.4 Hz, 2H), 7.36 (s, 1H), 7.25 (d, J=7.1 Hz, 1H), 6.45 (s, 1H), 6.02 (br, 1H), 3.20 (br, 2H), 3.03 (m, 6H), 2.65 (s, 3H), 2.22 (m, 2H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C28H29N7O3: 512.23 (M+H), Found: 512.1.

Workup

  1. customprepared
  2. customPurification by preparative HPLC (32 mL/min, 5-100% H2O/MeCN (0.01% TFA, v/v) gradient over 10 min)

Sources & evidence

ORD record
ord-174e72391d3744be9d03f72598b14668
Source dataset
uspto-grants-2010_01
Patent number
US07642270B2

Reaction notes

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