Sodium Chloride → 4-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide

HRID 23434Notes

Reaction equation

HRID 23434 reaction equation
[O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[NH:6][N:5]=[C:4]([C:11]([OH:13])=O)[C:3]1=2.Cl.CN(C)CCCN=C=NCC.[CH2:26]([N:28]([CH2:40][CH3:41])[CH2:29][CH2:30][CH2:31][O:32][C:33]1[N:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=1)[CH3:27].[Na+].[Cl-].C(=O)([O-])[O-].[Na+].[Na+]>CN(C1C=CN=CC=1)C.ClCCl.CN(C=O)C>[CH2:40]([N:28]([CH2:26][CH3:27])[CH2:29][CH2:30][CH2:31][O:32][C:33]1[N:38]=[CH:37][C:36]([NH:39][C:11]([C:4]2[C:3]3[C:2](=[O:1])[CH2:10][CH2:9][CH2:8][C:7]=3[NH:6][N:5]=2)=[O:13])=[CH:35][CH:34]=1)[CH3:41]

Participants

9

Reactant 5

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 114239274-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acidHCID 225742766-(3-Diethylamino-propoxy)-pyridin-3-ylamine

Product 1

HCID 102934674-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A solution of 4-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid (2.25 g, 12 mmol), 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (2.87 g, 15 mmol), DMAP (1.83 g, 15 mmol), and DMF (10 mL) in dichloromethane (40 mL) is stirred under nitrogen at 20° C. for 2 hours. 6-(3-Diethylamino-propoxy)-pyridin-3-ylamine (2.50 g, 11.2 mmol) is added. The mixture is stirred under nitrogen at 40° C. for 24 hours; and then poured into 10% NaCl, treated with 1 M sodium carbonate to pH 10, and extracted with chloroform (100 mL). The solution is concentrated, diluted with xylenes (100 mL), and the volatiles are thoroughly evaporated under reduced pressure. The residue is purified by column chromatography on silica gel using a mixture of chloroform-methanol-30% ammonium hydroxide (90:9:1, v/v/v) as an eluent and the residue is recrystallized from ethyl acetate to give pure 4-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [6-(3-diethylamino-propoxy)-pyridin-3-yl]-amide. 1H NMR (CD3OD) t, J=7.1 Hz, 6H), 1.97 (m, 2H), 2.25 (quintet, J=6.3 Hz, 2H), 2.62 (q, J=7.1 Hz, 4H), 2.71 (m, 4H), 2.99 (t, J=6.3 Hz, 2H), 4.03 (t, J=6.3 Hz, 2H), 6.81 (dd, J=8.9 and 0.5 Hz, 1H), 8.12 (dd, J=8.9 and 2.7 Hz, 1H), 8.56 (dd, J=2.7 and 0.5 Hz, 1H). MW 385.471; MS (M−H)− 384.

Workup

  1. extractionextracted with chloroform (100 mL)
  2. concentrationThe solution is concentrated
  3. additiondiluted with xylenes (100 mL)
  4. customthe volatiles are thoroughly evaporated under reduced pressure
  5. customThe residue is purified by column chromatography on silica gel using
  6. additiona mixture of chloroform-methanol-30% ammonium hydroxide (90:9:1, v/v/v) as an eluent
  7. customthe residue is recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-3dd516a960d3493aa634626ac6bd813a
Source dataset
uspto-grants-2005_02
Patent number
US06852730B2

Reaction notes

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