Dimethylformamide → (2-(4-(3-hydroxy-1-adamantylcarbonylamino)-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide oxalate

HRID 482596Notes

Reaction equation

HRID 482596 reaction equation
[OH:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][C:4]([C:12](O)=[O:13])([CH2:5]3)[CH2:3]1)[CH2:9]2.C(N1[CH:26]=[CH:25][N:24]=[CH:23]1)(N1C=CN=C1)=O.[C:27]([OH:32])(=[O:31])[C:28]([OH:30])=[O:29].[C:33](O)(=O)[C:34](O)=O.NC1CCN(CC[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])CC1.C[N:64]([CH3:67])C=O>>[C:27]([OH:32])(=[O:31])[C:28]([OH:30])=[O:29].[OH:1][C:2]12[CH2:9][CH:8]3[CH2:7][CH:6]([CH2:5][C:4]([C:12]([NH:64][CH:67]4[CH2:27][CH2:23][N:24]([CH2:33][CH2:34][C:58]5[CH:57]=[CH:56][CH:55]=[C:54]6[C:59]=5[C:51]([C:49]([NH2:48])=[O:50])=[N:52][N:53]6[CH:60]([CH3:61])[CH3:62])[CH2:25][CH2:26]4)=[O:13])([CH2:10]3)[CH2:3]1)[CH2:11]2

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 682631,1'-CarbonyldiimidazoleHCID 27365183-Hydroxyadamantane-1-carboxylic acidHCID 86751129N-[2-(4-amino-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide dioxalate

Product 1

HCID 86753047(2-(4-(3-hydroxy-1-adamantylcarbonylamino)-1-piperidinyl)ethyl]-1-(2-propyl)-1H-indazole-3-carboxamide oxalateYield 47%

Procedure

A mixture of 1.07 g (5.45 mmol) of 3-hydroxy-1-adamantylcarboxylic acid and 0.88 g (5.45 mmol) of 1,1'-carbonyldiimidazole in 10 mL of dimethylformamide was stirred for 2 hours at ambient temperature. To this solution was dropwise added 1.80 g (5.45 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 1.30 g (47%) of the desired product as a foam. Further treatment of the product with 0.23 g (2.62 mmol) of oxalic acid in 20 mL of ethanol provided, upon concentration of the solution, 1.51 g of the oxalate salt (LSN343031). 1H NMR (500 MHz, DMSO-d6) d 8.51 (t, 1H), 8.19 (d, 1H), 7.9 (br s, 3H), 7.78 (d, 1H), 7.44 (t, 1H), 7.40 (d, 1H), 7.27 (t, 1H), 5.06 (m, 1H), 3.84 (m, 1H), 3.72 (m, 2H), 3.52 (m, 2H), 3.24 (br t, 2H), 3.07 (br t, 2H), 2.11 (br s, 2H), 1.82 (m, 4H), 1.64 (m, 6H), 1.55 (m, 10H), 1.48 (br s, 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-66a9edb2e6994fec8280e9570372518d
Source dataset
uspto-grants-1998_08
Patent number
US05798367

Reaction notes

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