1,2-Dichloroethane → 2',4'-Difluoro-5-piperazin-1-yl-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}biphenyl-3-carboxamide

HRID 888389Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 888389
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([C:28]([OH:30])=O)[CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[F:27])[CH:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.Cl.[F:33][C:34]([F:45])([F:44])[C:35]1[N:40]=[CH:39][C:38]([C@H:41]([NH2:43])[CH3:42])=[CH:37][N:36]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl>CN(C)C=O>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C:18]1[CH:19]=[C:14]([N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[CH:15]=[C:16]([C:28]([NH:43][C@@H:41]([C:38]2[CH:37]=[N:36][C:35]([C:34]([F:45])([F:44])[F:33])=[N:40][CH:39]=2)[CH3:42])=[O:30])[CH:17]=1

Komponenten

8

Edukt 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66690185(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethanamine dihydrochlorideHCID 684965535-[4-(Tert-butoxycarbonyl)piperazin-1-yl]-2',4'-difluorobiphenyl-3-carboxylic acid

Produkt 1

HCID 426029932',4'-Difluoro-5-piperazin-1-yl-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}biphenyl-3-carboxamideAusbeute 80,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2′,4′-difluorobiphenyl-3-carboxylic acid (30.0 mg, 0.072 mmol), in N,N-dimethylformamide (1.0 mL) was added (1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethanamine dihydrochloride (22.7 mg, 0.086 mmol), EDC (17.8 mg, 0.093 mmol), HOBT (11.0 mg, 0.072 mmol) and diisopropylethylamine (0.038 mL, 0.215 mmol). After 16 h, the mixture was acidified with hydrochloric acid gas. After 15 min, the mixture was concentrated and purified by reverse phase HPLC (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid) to give the title compound (28.4 mg). HRMS 492.1833 (M+1). 1H NMR (500 MHz, CD3OD): δ 9.00 (s, 2H); 7.57-7.50 (m, 1H); 7.47-7.43 (m, 2H); 7.24 (q, J=1.7 Hz, 1H); 7.09-7.03 (m, 2H); 5.33 (q, J=7.1 Hz, 1H); 3.25 (t, J=4.9 Hz, 4H); 3.00 (t, J=4.7 Hz, 4H); 1.68 (d, J=7.2 Hz, 3H).

Aufarbeitung

  1. waitAfter 15 min
  2. concentrationthe mixture was concentrated
  3. custompurified by reverse phase HPLC (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-6ee96bed8d394fe88d76d173f770c92a
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08247401B2

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