Triethylamine → 2-(3-Imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid methoxy-amide

HRID 12346

Reaction equation

HRID 12346 reaction equation
C(N(CC)CC)C.Cl.[CH3:9][O:10][NH2:11].C([O:14][C:15]([C:17]1[C:18](=[O:45])[C:19]2[CH:24]=[N:23][C:22]([NH:25][CH2:26][CH2:27][CH2:28][N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)=[N:21][C:20]=2[N:34]([C:36]2[CH:37]=[C:38]3[C:42](=[CH:43][CH:44]=2)[CH2:41][CH2:40][CH2:39]3)[CH:35]=1)=O)C>CO.O>[CH3:9][O:10][NH:11][C:15]([C:17]1[C:18](=[O:45])[C:19]2[CH:24]=[N:23][C:22]([NH:25][CH2:26][CH2:27][CH2:28][N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)=[N:21][C:20]=2[N:34]([C:36]2[CH:37]=[C:38]3[C:42](=[CH:43][CH:44]=2)[CH2:41][CH2:40][CH2:39]3)[CH:35]=1)=[O:14]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 685831992-(3-Imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester

Product 1

HCID 160494442-(3-Imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid methoxy-amide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Triethylamine (0.5 mL) was added to a mixture of O-methylhydroxylamine hydrochloride (220 mg) and 2-(3-imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (Example 3 Step A, 3.0 mg, 0.006 mmol) in 0.5 mL of methanol. The reaction mixture was kept in a sealed tube at 110° C. for 2 days with stirring. After cooling to room temperature the solution was diluted with water and extracted with dichloromethane. The crude product, after concentration, was loaded to HPLC for purification (32 mL/min 5-100% MeCN/H2O gradient over 10 min). 2-(3-Imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid methoxy-amide was obtained as a white solid (1.9 mg, 65%). 1H NMR (400 MHz, CDCl3) δ (ppm): 11.98 (br, 1H), 9.28 (s, 1H), 8.75 (s, 1H), 7.32 (d, J=7.8 Hz, 1H), 7.21 (s, 1H), 7.14 (d, J=7.8 Hz, 1H), 7.03 (br, 2), 6.74 (s, 1H), 5.80 (br, 1H), 3.89 (s, 3H), 3.00 (m, 8H), 2.17 (m, 2H), 1.92 (m, 2H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C24H25N7O3: 460.20 (M+H). Found. 460.2.

Workup

  1. extractionextracted with dichloromethane
  2. concentrationThe crude product, after concentration
  3. customwas loaded to HPLC for purification (32 mL/min 5-100% MeCN/H2O gradient over 10 min)

Sources & evidence

ORD record
ord-586bc51c127c4e3c8344b2f9a0952509
Source dataset
uspto-grants-2010_06
Patent number
US07728003B2

Linked notes

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