1,2-Dichloroethane → N'-{1-[(1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarbonyl)-amino]-cyclopropanecarbonyl}-hydrazinecarboxylic acid tert-butyl ester

HRID 1040558ノート

反応式

HRID 1040558 の反応式
[C:1]([C:3]1[CH:36]=[CH:35][C:6]([CH2:7][C@@:8]2([CH3:34])[N:12]3[C:13]([C:16]([NH:18][C:19]4([C:22]([OH:24])=O)[CH2:21][CH2:20]4)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=3)[C:9]2=[O:33])=[CH:5][CH:4]=1)#[N:2].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(CC)CC.[C:58]([O:62][C:63]([NH:65][NH:66][C:67]([C:69]1([NH2:72])[CH2:71][CH2:70]1)=[O:68])=[O:64])([CH3:61])([CH3:60])[CH3:59]>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[C:58]([O:62][C:63]([NH:65][NH:66][C:67]([C:69]1([NH:72][C:22]([C:19]2([NH:18][C:16]([C:13]3[N:12]4[C@@:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:36][CH:35]=5)([CH3:34])[C:9](=[O:33])[N:10]([C:25]5[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=5)[C:11]4=[N:15][CH:14]=3)=[O:17])[CH2:20][CH2:21]2)=[O:24])[CH2:71][CH2:70]1)=[O:68])=[O:64])([CH3:61])([CH3:59])[CH3:60]

参加物

9

反応物 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 584309681-{[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acidHCID 67390113N'-(1-amino-cyclopropanecarbonyl)-hydrazinecarboxylic acid tert-butyl ester

生成物 1

HCID 58430863N'-{1-[(1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarbonyl)-amino]-cyclopropanecarbonyl}-hydrazinecarboxylic acid tert-butyl ester収率 96%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid (0.25 g, 0.48 mmol) in DMF (2 mL) was added HOAt (0.065 g, 0.48 mmol), EDC (0.092 g, 0.48 mmol), DMAP (0.005 g, 0.041 mmol), Et3N (0.066 mL, 0.48 mmol). The reaction allowed to stir for 10 min at room temperature. To this mixture was added N′-(1-amino-cyclopropanecarbonyl)-hydrazinecarboxylic acid tert-butyl ester (0.10 g, 0.48 mmol) and the reaction was heated at 70° C. for 15 h. The mixture was cooled to room temperature, diluted with water and extracted with EtOAc (3×50 mL). The combined extracts were washed with saturated NaHCO3, 2N HCl, brine and dried with MgSO4. The mixture was filtered and concentrated in vacuo to give N′-{1-[(1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarbonyl)-amino]-cyclopropanecarbonyl}-hydrazinecarboxylic acid tert-butyl ester (0.33 g, 96%) as a yellow solid, m/z 721.9 [M+1]+.

後処理

  1. temperaturethe reaction was heated at 70° C. for 15 h
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined extracts were washed with saturated NaHCO3, 2N HCl, brine
  5. dry with materialdried with MgSO4
  6. filtrationThe mixture was filtered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-68e211e9d2c643ae9c011aeab7a535c2
出典データセット
uspto-grants-2013_10
特許番号
US08552205B2

反応ノート

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