1,2-Dichloroethane → (R)-benzyl 1-(1-cyano-7-(4-methylpiperazine-1-carbonyl)-9H-carbazol-4-yl)piperidin-3-ylcarbamate

HRID 1811098

Reaktionsgleichung

Reaktionsgleichung von HRID 1811098
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]3[C:19]=2[C:20]2[CH:21]=[CH:22][C:23]([C:33](O)=[O:34])=[CH:24][C:25]=2[NH:26]3)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:50][N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>C1COCC1.C(Cl)Cl.CN(C=O)C>[C:31]([C:28]1[C:27]2[NH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:33]([N:54]4[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]4)=[O:34])[CH:24]=3)[C:19]=2[C:18]([N:14]2[CH2:15][CH2:16][CH2:17][C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:13]2)=[CH:30][CH:29]=1)#[N:32]

Komponenten

6

Edukt 4

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 66605842(R)-5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylic acid

Produkt 1

HCID 86642947(R)-benzyl 1-(1-cyano-7-(4-methylpiperazine-1-carbonyl)-9H-carbazol-4-yl)piperidin-3-ylcarbamateAusbeute 39,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 86642945dichloromethane tetrahydrofuran DMFLösungsmittel

Versuchsvorschrift

Step 4 A solution of (R)-5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylic acid (130 mg, 0.277 mmol), EDC (74.5 mg, 0.388 mmol), HOBT (59.5 mg, 0.388 mmol), and 1-methylpiperazine (0.092 mL, 0.832 mmol) in THF-DCM-DMF (4:1:1, 6 mL) was stirred at rt over a weekend. The mixture was concentrated and partitioned between EtOAc and NaHCO3 (aq). The organic phase was washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 100:0 to 92.5:7.5 DCM-2 M methanolic ammonia) to provide (R)-benzyl 1-(1-cyano-7-(4-methylpiperazine-1-carbonyl)-9H-carbazol-4-yl)piperidin-3-ylcarbamate as a yellow solid (60 mg). 1H NMR (400 MHz, DMSO-d6) δ 12.31 (s, 1H) 8.09 (d, J=8.13 Hz, 1H) 7.82 (d, J=8.35 Hz, 1H) 7.64 (s, 1H) 7.49 (d, J=7.69 Hz, 1H) 7.24-7.40 (m, 6 H) 6.93 (d, J=8.35 Hz, 1H) 4.87-5.11 (m, 2H) 3.00-3.96 (m, 12H) 2.83 (s, 3H) 2.55-2.70 (m, 1H) 1.73-2.08 (m, 3H) 1.34-1.57 (m, 1H).). Mass spectrum m/z 551.2 (M+H)+.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. custompartitioned between EtOAc and NaHCO3 (aq)
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (
  7. washeluting with a gradient from 100:0 to 92.5:7.5 DCM-2 M methanolic ammonia)

Quellen und Nachweise

ORD-Eintrag
ord-068e6a015e4c4474ba2e04bcf7bc0d8d
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362065B2

Verknüpfte Notizen

Wird geladen…