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Benzenesulfonyl chloride → {1-[1'-Benzenesulfonyl-5-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1',2',4',5'-tetrahydro-1H-[2,4']biimidazolyl-3'-carbonyl]-2-methyl-propyl]-carbamic acid methyl ester

HRID 417514
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 417514
[CH3:1][O:2][C:3](=[O:37])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=3)[N:20]=2)[CH2:14][N:13]([S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].COC(=O)NC(C(N1C(C2NC=C(C3C=CC(Br)=CC=3)N=2)CN(C(=O)C)C1)=O)C(C)C.C1(S(Cl)(=O)=O)C=CC=CC=1.[CH3:79][O:80][C:81](=[O:114])[NH:82][CH:83]([C:87]([N:89]1[CH2:93][CH2:92][CH2:91][CH:90]1[C:94]1[NH:95][CH:96]=[C:97]([C:99]2[CH:104]=[CH:103][C:102](B3OC(C)(C)C(C)(C)O3)=[CH:101][CH:100]=2)[N:98]=1)=[O:88])[CH:84]([CH3:86])[CH3:85].C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.COCCOC>[CH3:1][O:2][C:3](=[O:37])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:102]4[CH:103]=[CH:104][C:99]([C:97]5[NH:98][C:94]([CH:90]6[CH2:91][CH2:92][CH2:93][N:89]6[C:87](=[O:88])[CH:83]([NH:82][C:81]([O:80][CH3:79])=[O:114])[CH:84]([CH3:86])[CH3:85])=[N:95][CH:96]=5)=[CH:100][CH:101]=4)=[CH:23][CH:22]=3)=[CH:18][N:17]=2)[CH2:14][N:13]([S:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 5

HCID 7369Benzenesulfonyl chlorideHCID 11430Potassium CarbonateHCID 178502159HCID 178502159, VerbindungHCID 178502205HCID 178502205, VerbindungHCID 178502209HCID 178502209, Verbindung

Produkt 1

HCID 66620333
{1-[1'-Benzenesulfonyl-5-(4'-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1',2',4',5'-tetrahydro-1H-[2,4']biimidazolyl-3'-carbonyl]-2-methyl-propyl]-carbamic acid methyl ester
Ausbeute 0 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

{1-[1′-Benzenesulfonyl-4-(4-bromo-phenyl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (63.1 mg, 106.9 mmol) [prepared as described for the synthesis of {1-[1′-Acetyl-4-(4-bromo-phenyl)-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (Example BY)]substituting the acetic anhydride with phenyl sulfonyl chloride] was combined with [2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (53.1 mg, 106.9 mmol) under an argon atmosphere. Potassium carbonate (29.2 mg, 0.212 mmol) and Pd(PPh3)4 (12.2 mg, 0.0106 mmol) were added, followed by DME (2.5 mL) and water (0.8 mL). The mixture was heated under microwave conditions for 20 minutes at 120° C. All volatiles were removed in vacuo and the crude material was dissolved in DMF and purified via RP-HPLC (eluent: water/MeCN w 0.1% TFA) to yield the product {1-[1′-Benzenesulfonyl-5-(4′-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1′,2′,4′,5′-tetrahydro-1H-[2,4]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (27.9 mg): LCMS-ESI+: calc'd for C45H53N9O8S: 880.2 (M+). Found: 881.5 (M+H+); 1H-NMR: 300 MHz, (MeOH-d4) δ: 8.01 (d, J=7.5 Hz, 2H), 7.90-7.76 (m, 11H), 7.65 (t, J=7.8 Hz, 2H), 5.59 (d, J=8.7 Hz, 1H), 5.25 (dd, J=7.5, 7.5 Hz, 1H), 5.19 (d, J=8.7 Hz, 1H), 4.67 (dd, J=7.5, 7.5 Hz, 1H), 4.32-4.22 (m, 2H), 4.08 (m, 2H), 3.85 (m, 1H), 3.68 (s, 3H), 3.66 (s, 3H), 3.44 (d, J=6.6 Hz, 1H), 2.57 (m, 1H), 2.29-1.99 (m, 5H), 0.99-0.86 (m, 12H).

Aufarbeitung

  1. customAll volatiles were removed in vacuo
  2. dissolutionthe crude material was dissolved in DMF
  3. custompurified via RP-HPLC (eluent: water/MeCN w 0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-92123fcfd92e40028d6196be97b1c334
Quelldatensatz
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08088368B2

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