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

HRID 2256374
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HRID 2256374 반응식
[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
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참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매
2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-89f128b306c04fa4bf8782870ca689e6
출처 데이터셋
uspto-grants-1997_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05654320

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