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

HRID 1096858
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1096858
[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][O:33][CH2:34][CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])=[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:75]1([NH:78][CH2:79][C:80]2[CH:85]=[CH:84][CH:83]=[C:82]([Cl:86])[C:81]=2[Cl:87])[CH2:77][CH2:76]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])([CH3:23])[CH3:22])=[O:18])[CH:10]([CH2:11][C:12]([C:27]3[S:31][C:30]([CH2:32][O:33][CH2:34][CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:41])[CH3:42])([CH3:38])[CH3:39])=[N:29][CH:28]=3)=[C:13]2[C:24](=[O:25])[N:78]([CH:75]2[CH2:76][CH2:77]2)[CH2:79][C:80]2[CH:85]=[CH:84][CH:83]=[C:82]([Cl:86])[C:81]=2[Cl:87])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
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Komponenten

8

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 834599Cyclopropyl-(2,3-dichloro-benzyl)-amine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 685735637-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester

Produkt 1

HCID 685707897-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazol-5-yl}-6-[cyclopropyl-(2,3-dichlorobenzyl)carbamoyl]-3,9-diazabicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl esterAusbeute 12,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred sol. of compound D8 (0.38 g, 0.594 mmol) in CH2Cl2 (3.0 mL) were added EDC.HCl (0.285 g, 1.49 mmol), HOBt (0.109 g, 0.713 mmol), DMAP (2.0 mg, 0.15 mmol) and DIPEA (0.467 mL, 2.67 mmol). After 15 min cyclopropyl-(2,3-dichloro-benzyl)amine (0.257 g, 1.19 mmol) was added and stirring was continued for 7 days. Every day cyclopropyl-(2,3-dichlorobenzyl)amine (prepared by reductive amination from 2,3-dichlorobenzaldehyde and cyclopropylamine, 0.128 g, 0.59 mmol) was added. The reaction mixture was partitioned between aq. 1M HCl and CH2Cl2, and the phases were separated, washed with aq. sat. NaHCO3, dried over MgSO4, filtered, and the solvents were removed in vacuo. Purification of the crude by FC (heptane/EtOAc 7/3→1/1) yielded the title product (60 mg, 12%) as a yellow oil. LC-MS: tR=1.28 min, ES+: 837.48.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-8ac95e8aceab44728a31653e054e6a40
Quelldatensatz
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08138340B2

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