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

HRID 1096857
ノート
印刷プレビュー

反応式

HRID 1096857 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]([CH2:32][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].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.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]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[S:31][C:30]([CH2:32][CH2:33][CH2:34][O:35][Si:36]([C:39]([CH3:41])([CH3:40])[CH3:42])([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])([CH3:4])([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 757711-Hydroxybenzotriazole2 回HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58006030Cyclopropyl-(2-methyl-3-methoxybenzyl)amine2 回HCID 685729567-{2-[3-(tert-Butyldimethylsilanyloxy)propyl]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 685705247{2-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-5-yl}-6-[cyclopropyl-(3-methoxy-2-methylbenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester収率 56.2%

試薬・触媒・溶媒 2

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

実験手順

To a stirred sol. of compound D6 (2.66 g, 4.26 mmol) in CH2Cl2 (45 mL) were added EDC.HCl (2.04 g, 10.6 mmol), HOBt (783 mg, 5.11 mmol), DMAP (13 mg, 0.107 mmol), and DIPEA (3.35 mL, 19.19 mmol). After 15 min cyclopropyl-(3-methoxy-2-methyl-benzyl)amine (prepared by reductive amination from 3-methoxy-2-methylbenzaldehyde, Comins, D. L.; Brown, J. D., J. Org. Chem., 1989, 54, 3730 and cyclopropylamine, 2.45 g, 12.80 mmol) was added and stirring was continued over 6 days. Three times were added cyclopropyl-(3-methoxy-2-methyl-benzyl)amine (817 mg, 4.27 mmol) and HOBt (392 mg, 2.55 mmol). The reaction mixture was partitioned between aq. 1M HCl and CH2Cl2, and the phases were separated. The org. layer was washed with aq. sat. NaHCO3, dried over MgSO4, filtered, and the solvents were removed in vacuo. Purification by FC (heptane/EtOAc 7/3→1/1) yielded the title product (1.91 g, 56%). LC-MS: tR=1.27 min, ES+: 797.59.

後処理

  1. customThe reaction mixture was partitioned between aq. 1M HCl and CH2Cl2
  2. customthe phases were separated
  3. washlayer was washed with aq. sat. NaHCO3
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed in vacuo
  7. customPurification by FC (heptane/EtOAc 7/3→1/1)

出典と根拠

ORDレコード
ord-29f2028576194208930c6f2c8fd494e2
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08138340B2

反応ノート

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