1,2-Dichloroethane → tert-Butyl 4-(5-((5S)-3-(3,3-dimethylbutyl)-4-oxo-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidin-1-yl)ethyl)thiazolidin-2-yl)thiazol-2-yl)piperidine-1-carboxylate

HRID 1695924

Reaktionsgleichung

Reaktionsgleichung von HRID 1695924
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][C:16]([CH:19]3[N:23]([CH2:24][CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:22](=[O:30])[C@H:21]([CH2:31][C:32](O)=[O:33])[S:20]3)=[CH:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[NH:58]1[CH2:63][CH2:62][CH:61]([N:64]2[CH2:70][CH2:69][C:68]3[CH:71]=[CH:72][CH:73]=[CH:74][C:67]=3[NH:66][C:65]2=[O:75])[CH2:60][CH2:59]1>C(Cl)Cl>[CH3:29][C:26]([CH3:28])([CH3:27])[CH2:25][CH2:24][N:23]1[C:22](=[O:30])[C@H:21]([CH2:31][C:32](=[O:33])[N:58]2[CH2:59][CH2:60][CH:61]([N:64]3[CH2:70][CH2:69][C:68]4[CH:71]=[CH:72][CH:73]=[CH:74][C:67]=4[NH:66][C:65]3=[O:75])[CH2:62][CH2:63]2)[S:20][CH:19]1[C:16]1[S:15][C:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[N:18][CH:17]=1

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 577743682-((5S)-2-(2-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiazol-5-yl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid

Produkt 1

HCID 25207442tert-Butyl 4-(5-((5S)-3-(3,3-dimethylbutyl)-4-oxo-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3(2H)-yl)piperidin-1-yl)ethyl)thiazolidin-2-yl)thiazol-2-yl)piperidine-1-carboxylateAusbeute 75,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 2-((5S)-2-(2-(1-(tert-Butoxycarbonyl)piperidin-4-yl)thiazol-5-yl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid (360 mg, 0.7 mmol, 1 eq) in DCM (8 mL) was added HOBt (162 mg, 1.06 mmol, 1.5 eq), EDC (202 mg, 1.06 mmol, 1.5 eq), DIEA (364 mg, 2.8 mmol, 4 eq) and 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (207 mg, 0.84 mmol, 1.2 eq). The resulting mixture was stirred at room temperature for 18 hr. The reaction mixture was diluted with DCM (10 mL) and washed with water (5 mL), brine (5 mL), dried (MgSO4) then concentrated in vacuo. The residue was purified by column chromatography over silica gel eluted with 0 to 10% MeOH in DCM to afford 390 mg of compound I-492 in 75% yield. (M+1) 739. 1H NMR (CDCl3) δ 7.19-6.91 (m, 5H), 6.75 (d, J=7.8 Hz, 1H), 5.68 (m, 1H), 4.75 (m, 1H), 4.47 (m, 1H), 4.18 (m, 1H), 3.93 (m, 1H), 3.46-2.67 (m, 11H), 2.08 (m, 6H), 1.71 (m, 6H), 1.47 (m, 9H), 0.85 (m, 9H) ppm.

Aufarbeitung

  1. washwashed with water (5 mL), brine (5 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationthen concentrated in vacuo
  4. customThe residue was purified by column chromatography over silica gel
  5. washeluted with 0 to 10% MeOH in DCM

Quellen und Nachweise

ORD-Eintrag
ord-afcf4fb36709467185c2eb51c99e636b
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08163737B2

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