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1-Hydroxybenzotriazole → 7-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]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 1096859
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1096859
[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]([O:86][CH3:87])[C:81]=2[CH3:88])[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]([CH3:23])([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:25])[N:78]([CH:75]2[CH2:77][CH2:76]2)[CH2:79][C:80]2[CH:85]=[CH:84][CH:83]=[C:82]([O:86][CH3:87])[C:81]=2[CH3:88])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
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Komponenten

8

Edukt 5

HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58006030Cyclopropyl-(2-methyl-3-methoxybenzyl)amine2×HCID 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 685723547-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]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 esterAusbeute 33,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirred sol. of the compound D8 (2.75 g, 4.30 mmol) in CH2Cl2 (21.5 mL) were added EDC.HCl (2.06 g, 10.75 mmol), HOBt (0.789 g, 5.16 mmol), DMAP (13 mg, 0.108 mmol), and DIPEA (3.378 mL, 19.3 mmol). After 15 min 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, 2.47 g, 12.9 mmol) was added, and stirring was continued over 7 days. Three times were added cyclopropyl-(3-methoxy-2-methylbenzyl)amine (823 mg, 4.30 mmol), and HOBt (290 mg, 2.15 mmol), and once was added DIPEA (3.38 mL, 19.3 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 of the residue by FC (heptane/EtOAc 7/3) yielded an impure product, which was purified again by HPLC. The title compound (1.16 g, 33%) was obtained as a yellow oil. LC-MS: tR=1.26 min, ES+: 813.59.

Aufarbeitung

  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 of the residue by FC (heptane/EtOAc 7/3)
  8. customyielded an impure product, which
  9. customwas purified again by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-175120fc0a1d4a61a2f4e15266e1c48f
Quelldatensatz
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08138340B2

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