1-Hydroxybenzotriazole → 7-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxy]thiazol-5-yl}-6-[cyclo-propyl-(2,3-dichlorobenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

HRID 1096853ノート

反応式

HRID 1096853 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[S:31][C:30]([O:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[N:29][CH:28]=3)=[C:13]2[C:24](O)=[O:25])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C.[CH:74]1([NH:77][CH2:78][C:79]2[CH:84]=[CH:83][CH:82]=[C:81]([Cl:85])[C:80]=2[Cl:86])[CH2:76][CH2:75]1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[S:31][C:30]([O:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:41])([CH3:42])[CH3:40])([CH3:38])[CH3:37])=[N:29][CH:28]=3)=[C:13]2[C:24](=[O:25])[N:77]([CH:74]2[CH2:75][CH2:76]2)[CH2:78][C:79]2[CH:84]=[CH:83][CH:82]=[C:81]([Cl:85])[C:80]=2[Cl:86])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 834599Cyclopropyl-(2,3-dichloro-benzyl)-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 685733277-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxy]thiazol-5-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester

生成物 1

HCID 685707807-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxy]thiazol-5-yl}-6-[cyclo-propyl-(2,3-dichlorobenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester収率 42%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

実験手順

A sol. of compound D4 (1.39 mmol, 0.87 g) in CH2Cl2 (11.2 mL) was treated with DMAP (0.35 mmol, 42 mg), HOBt (1.67 mmol, 0.23 g), EDC.HCl (3.47 mmol, 0.66 g), and DIPEA (5.55 mmol, 0.95 mL). After 30 min at rt, cyclopropyl-(2,3-dichlorobenzyl)-amine (prepared by reductive amination from 2,3-dichlorobenzaldeyhde and cyclopropylamine; 4.16 mmol, 0.90 g) was added and the mixture was stirred for 4 days at rt. The reaction was then diluted with CH2Cl2 (40 mL), washed with aq. 1M HCl (2×50 mL), dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 30:70) yielded the title compound (0.48 g, 42%). LC-MS: tR=1.29 min; ES+: 823.50.

後処理

  1. washwashed with aq. 1M HCl (2×50 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customPurification of the residue by FC (EtOAc/heptane 30:70)

出典と根拠

ORDレコード
ord-0346bf2d8d6148dabb7ab34322d75cf4
出典データセット
uspto-grants-2012_03
特許番号
US08138340B2

反応ノート

読み込み中…