Sodium Carbonate → Phenylmethyl (2S)-4-({2'-fluoro-5'-[({[3-(4-piperidinyl)phenyl]carbonyl}amino)methyl]-3-biphenylyl}methyl)-2-methyl-1-piperazinecarboxylate

HRID 2080325Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2080325
CC(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17]([OH:19])=O)[CH2:10][CH2:9]1)=O)(C)C.[NH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]([F:55])=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][N:38]3[CH2:43][CH2:42][N:41]([C:44]([O:46][CH2:47][C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[O:45])[C@@H:40]([CH3:54])[CH2:39]3)[CH:32]=2)[CH:30]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O>[F:55][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][NH:23][C:17]([C:16]2[CH:20]=[CH:21][CH:22]=[C:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH:15]=2)=[O:19])=[CH:30][C:29]=1[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][N:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:45])[C@@H:40]([CH3:54])[CH2:39]2)[CH:32]=1

Komponenten

8

Edukt 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450737913-(1-(tert-Butoxycarbonyl)piperidin-4-yl)benzoic acidHCID 57730446Phenylmethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

Produkt 1

HCID 57736691Phenylmethyl (2S)-4-({2'-fluoro-5'-[({[3-(4-piperidinyl)phenyl]carbonyl}amino)methyl]-3-biphenylyl}methyl)-2-methyl-1-piperazinecarboxylateAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of the commercially available 3-(1-{[(1,1-dimethylethyl)oxy]carbonyl}-4-piperidinyl)benzoic acid (183 mg, 0.60 mmol) in 2 mL of dry DMF was added phenylmethyl (2S)-4-{[5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (250 mg, 0.60 mmol), DIPEA (0.2 ml, 1.4 mmol), and HATU (251 mg, 0.66 mmol). The reaction mixture was stirred at room temperature for 2 h before addition of 2 mL of saturated Na2CO3 and 10 mL of EtOAc. The organic layer was separated, dried over Na2SO4, and filtered. The filtrate was concentrated and the residue was mixed with 4M HCl in 1,4-dioxane (5 mL). The resulting mixture was stirred at room temperature for 1 h. After removal of the solvent, the residue was purified by Gilson reverse phase HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min), to give the title compound (162 mg, 43%). LC/MS: m/z, 635 (M+H), 1.75 min.

Aufarbeitung

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. additionthe residue was mixed with 4M HCl in 1,4-dioxane (5 mL)
  6. customAfter removal of the solvent
  7. customthe residue was purified by Gilson reverse phase HPLC
  8. washeluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min)

Quellen und Nachweise

ORD-Eintrag
ord-62c1683a158041a183376bf0584bc667
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07932247B2

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