Diisopropylethylamine → N-{(1R,3S,4S)-2-[2-Amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[2.2.1]hept-3-ylmethyl}-2,2,2-trifluoro-acetamide

HRID 882798Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 882798
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[C:27]([C:29]([OH:31])=O)[N:28]=1.[C@H:39]12[CH2:45][C@H:42]([CH2:43][CH2:44]1)[C@@H:41]([CH2:46][NH:47][C:48](=[O:53])[C:49]([F:52])([F:51])[F:50])[NH:40]2.CCN(C(C)C)C(C)C>CN(C=O)C.CC(OC)(C)C>[NH2:23][C:24]1[S:25][C:26]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)=[C:27]([C:29]([N:40]2[C@H:41]([CH2:46][NH:47][C:48](=[O:53])[C:49]([F:51])([F:52])[F:50])[C@@H:42]3[CH2:45][C@H:39]2[CH2:44][CH2:43]3)=[O:31])[N:28]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 574371792-Amino-5-(3-fluorophenyl)-1,3-thiazole-4-carboxylic acidHCID 86649701N-[(1R,3S,4S)-1-(2-Aza-bicyclo[2.2.1]hept-3-yl)methyl]-2,2,2-trifluoro-acetamide

Produkt 1

HCID 86649702N-{(1R,3S,4S)-2-[2-Amino-5-(3-fluoro-phenyl)-thiazole-4-carbonyl]-2-aza-bicyclo[2.2.1]hept-3-ylmethyl}-2,2,2-trifluoro-acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Versuchsvorschrift

TBTU (1.70 mmol, 1.10 eq) is added to a solution of 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid (1.62 mmol, 1.05 eq), N-[(1R,3S,4S)-1-(2-Aza-bicyclo[2.2.1]hept-3-yl)methyl]-2,2,2-trifluoro-acetamide (1.55 mmol, 1.0 eq) and DIPEA (5.41 mmol, 3.5 eq) in DMF (10 mL). After 90 min the mixture is diluted with TBME (50 mL) and washed three times with an aq. NaOH solution (0.5 M, 50 mL each). The combined aq. layers are extracted twice with TBME (30 mL each). The organic layers are combined, washed with water (3×30 mL) and brine (30 mL), dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.82 min; [M+H]+=442.9.

Aufarbeitung

  1. washwashed three times with an aq. NaOH solution (0.5 M, 50 mL each)
  2. extractionThe combined aq. layers are extracted twice with TBME (30 mL each)
  3. washwashed with water (3×30 mL) and brine (30 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-ea3351da984e48ac9d25900e0e2c29b5
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08236801B2

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