1,1'-Carbonyldiimidazole → N-[2-(4-(4-hydroxy-1-adamantylcarbonylamino)-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide oxalate

HRID 2256374Notes

Reaction equation

HRID 2256374 reaction equation
[OH:1][CH:2]1[CH:9]2[CH2:10][C:5]3([C:12]([OH:14])=O)[CH2:6][CH:7]([CH2:11][CH:3]1[CH2:4]3)[CH2:8]2.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:27]([OH:32])(=[O:31])[C:28]([OH:30])=[O:29].C(O)(=O)C(O)=O.[NH2:39][CH:40]1[CH2:45][CH2:44][N:43]([CH2:46][CH2:47][NH:48][C:49]([C:51]2[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[N:53]([CH:60]([CH3:62])[CH3:61])[N:52]=2)=[O:50])[CH2:42][CH2:41]1>CN(C)C=O>[C:27]([OH:32])(=[O:31])[C:28]([OH:30])=[O:29].[OH:1][CH:2]1[CH:9]2[CH2:10][C:5]3([C:12]([NH:39][CH:40]4[CH2:41][CH2:42][N:43]([CH2:46][CH2:47][NH:48][C:49]([C:51]5[C:59]6[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=6)[N:53]([CH:60]([CH3:62])[CH3:61])[N:52]=5)=[O:50])[CH2:44][CH2:45]4)=[O:14])[CH2:6][CH:7]([CH2:11][CH:3]1[CH2:4]3)[CH2:8]2

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 45525374-hydroxyadamantane-1-carboxylic AcidHCID 86751129N-[2-(4-amino-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide dioxalate

Product 1

HCID 18969242N-[2-(4-(4-hydroxy-1-adamantylcarbonylamino)-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide oxalateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 0.50 g (2.55 mmol) of 4-hydroxy-1-adamantylcarboxylic acid and 0.44 g (2.71 mmol) of 1,1'-carbonyldiimidazole in 10 mL of dimethylformamide was stirred for 2 hours at ambient temperature. To this solution was dropwise added 0.90 g (2.75 mmol) of the product of Example 23 in 7 mL of dimethylformamide. The reaction was stirred for 18 hours and then concentrated in vacuo, diluted with dichloromethane and solids removed by filtration. The crude product was purified by chromatography (silica, 9:1 dichloromethane-methanol) to provide 0.71 g (55%) of the desired product as a foam. Further treatment of 500 mg of the product with 88 mg of oxalic acid in 15 mL of ethanol provided, upon concentration of the solution, 580 mg of the oxalate salt (LSN343032). 1H NMR (300 MHz, DMSO-d6) d 8.47 (t, 1H), 8.11 (d, 1H), 7.75 (d, 1H), 7.40 (t, 1H), 7.28 (d, 1H), 7.21 (t, 1H), 6.3 (br s, 3H), 5.04 (m, 1H), 3.74 (m, 1H), 3.59 (m, 3H), 3.40 (m, 2H), 3.13 (m, 2H), 2.95 (m, 2H), 1.95 (d, 2H), 1.69 (m, 13H), 1.47 (d, 6H), 1.25 (d, 2H).

Workup

  1. stirringThe reaction was stirred for 18 hours
  2. concentrationconcentrated in vacuo
  3. additiondiluted with dichloromethane and solids
  4. customremoved by filtration
  5. customThe crude product was purified by chromatography (silica, 9:1 dichloromethane-methanol)

Sources & evidence

ORD record
ord-89f128b306c04fa4bf8782870ca689e6
Source dataset
uspto-grants-1997_08
Patent number
US05654320

Reaction notes

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