Triethylamine → tert-Butyl [(1R,3S)-3-(2-methoxyethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate

HRID 1044623Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1044623
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([CH2:17][CH2:18][O:19][CH3:20])([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([CH2:17][CH2:18][O:19][CH3:20])([C:14]([N:34]2[CH2:35][CH2:36][N:31]([C:27]3[CH:26]=[C:25]([C:24]([F:38])([F:23])[F:37])[CH:30]=[CH:29][N:28]=3)[CH2:32][CH2:33]2)=[O:16])[CH2:10]1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59833582(1S,3R)-3-[(tert-Butoxycarbonyl)amino]-1-(2-methoxyethyl)cyclopentanecarboxylic acidHCID 685975881-[4-(Trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride

Produkt 1

HCID 59833567tert-Butyl [(1R,3S)-3-(2-methoxyethyl)-3-(4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamateAusbeute 52,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(1S,3R)-3-[(tert-Butoxycarbonyl)amino]-1-(2-methoxyethyl)cyclopentanecarboxylic acid (276.6 mg, 0.96 mmol), 1-[4-(trifluoromethyl)pyridin-2-yl]piperazine dihydrochloride (322.0 rug, 1.06 mmol), triethylamine (0.54 mL, 3.85 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (547.6 mg, 1.44 mmol) (HBTU) were mixed in dry DMF (6.6 mL) and the resultanting brown solution was stirred at room temperature under N2 for three days. The reaction mixture was diluted with CH2Cl2, and washed with saturated Na2CO3. The aqueous layer was extracted with CH2Cl2 four times. The combined organic layers were dried (MgSO4), filtered, concentrated and purified by flash chromatography (EtOAc/Hexane) to provide the desired product (252 mg, 52%). MS calculated for C24H36F3N4O4 (M+H) 501.3; found 401.3 (M+H-Boc).

Aufarbeitung

  1. washwashed with saturated Na2CO3
  2. extractionThe aqueous layer was extracted with CH2Cl2 four times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (EtOAc/Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-97d49e9221924319b9ea08827be03ad3
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08563582B2

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