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

HRID 1096852

反応式

HRID 1096852 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]([O:85][CH3:86])[C:80]=2[CH3:87])[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]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[N:29][CH:28]=3)=[C:13]2[C:24](=[O:25])[N:77]([CH:74]2[CH2:76][CH2:75]2)[CH2:78][C:79]2[CH:84]=[CH:83][CH:82]=[C:81]([O:85][CH3:86])[C:80]=2[CH3:87])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58006030HCID 58006030、化合物HCID 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 685705317-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxy]thiazol-5-yl}-6-[cyclo-propyl-(3-methoxy-2-methylbenzyl)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 (7.76 mmol, 4.86 g) in CH2Cl2 (63 mL) was treated with DMAP (1.94 mmol, 0.27 mg), HOBt (9.31 mmol, 1.26 g), EDC.HCl (19.40 mmol, 3.72 g), and DIPEA (31.04 mmol, 5.31 mL). After 30 min at rt, cyclopropyl-(3-methoxy-2-methylbenzyl)amine (prepared by reductive amination from 3-methoxy-2-methylbenzaldehyde, Comins, D. L.; Brown, J. D., J. Org. Chem., 1989, 54, 3730 and cyclopropylamine, 23.28 mmol, 4.45 g) was added and the mixture was stirred for 4 days at rt. The reaction was then diluted with CH2Cl2 (140 mL), washed with aq. 1M HCl (2×100 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=1.27 min; ES+: 799.56.

後処理

  1. washwashed with aq. 1M HCl (2×100 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-ef0d3c1875c44b60a3ee86e158cb6235
出典データセット
uspto-grants-2012_03
特許番号
US08138340B2

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