1-Hydroxybenzotriazole → 1-Cyclobutyl-4-{[4-(1,1-dioxido-4-thiomorpholinyl)phenyl]carbonyl}hexahydro-1H-1,4-diazepine hydrochloride

HRID 2261236Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2261236
[ClH:1].Cl.[CH:3]1([N:7]2[CH2:13][CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.CCN(CC1C=CC=CC=1)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.C1C=CC2N(O)N=NC=2C=1.[O:54]=[S:55]1(=[O:70])[CH2:60][CH2:59][N:58]([C:61]2[CH:69]=[CH:68][C:64]([C:65](O)=[O:66])=[CH:63][CH:62]=2)[CH2:57][CH2:56]1>C(Cl)Cl.C(Cl)CCl>[ClH:1].[CH:3]1([N:7]2[CH2:13][CH2:12][CH2:11][N:10]([C:65]([C:64]3[CH:63]=[CH:62][C:61]([N:58]4[CH2:57][CH2:56][S:55](=[O:70])(=[O:54])[CH2:60][CH2:59]4)=[CH:69][CH:68]=3)=[O:66])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1

Komponenten

7

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27638174-(1,1-Dioxidothiomorpholino)benzoic acidHCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 574239521-Cyclobutyl-1,4-diazepane dihydrochloride

Produkt 1

HCID 669300931-Cyclobutyl-4-{[4-(1,1-dioxido-4-thiomorpholinyl)phenyl]carbonyl}hexahydro-1H-1,4-diazepine hydrochlorideAusbeute 30,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

1-(Cyclobutyl)-hexahydro-1H-1,4-diazepine dihydrochloride (D4) (0.15 g) was stirred with diethylaminomethyl polystyrene (1.0 g), HOBT (0.045 g), 4-(1,1-dioxido-4-thiomorpholinyl)benzoic acid (0.186 g) in DCM (5 ml). EDC (0.165 g) was then added and the reaction was stirred at rt for 16 h. The polymer supported base was filtered off and the filtrate was diluted with DCM (10 ml) and washed with saturated sodium hydrogen carbonate (2×15 ml). The organic layer was then loaded directly onto a silica column and eluted with 0-10% MeOH (containing 10% 0.880 ammonia solution)/DCM. The isolated free base product was dissolved in DCM (5 ml) and treated with excess 1N HCl/diethyl ether solution (1 ml) and stirred for 10 min. The mixture was evaporated (co-evaporated with acetone 2×10 ml), triturated with acetone, then dried at 50° C. under high vacuum for 16 h to yield the title compound (E9) as a pale solid (0.086 g). MS electrospray (+ion) 392 (MH+). 1H NMR δ (DMSO-d6): 10.5 (1H, s), 7.37 (2H, d, J=8.4 Hz), 7.07 (2H, d, J=8.8 Hz), 4.18-3.24 (10H, m), 3.11 (4H, m), 3.10-2.85 (2H, m), 2.45-1.98 (7H, m), 1.80-2.54 (2H, m).

Aufarbeitung

  1. filtrationwas filtered off
  2. additionthe filtrate was diluted with DCM (10 ml)
  3. washwashed with saturated sodium hydrogen carbonate (2×15 ml)
  4. washeluted with 0-10% MeOH (containing 10% 0.880 ammonia solution)/DCM
  5. dissolutionThe isolated free base product was dissolved in DCM (5 ml)
  6. additiontreated with excess 1N HCl/diethyl ether solution (1 ml)
  7. stirringstirred for 10 min
  8. customThe mixture was evaporated (co-evaporated with acetone 2×10 ml)
  9. customtriturated with acetone
  10. customdried at 50° C. under high vacuum for 16 h

Quellen und Nachweise

ORD-Eintrag
ord-e4d1d42da9e3447bb5d9b6e22d7b5fed
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07846922B2

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