2,6-Lutidine → HCID 67190452, Verbindung

HRID 546095Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 546095
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.[C:42]([O:46][C:47](=[O:62])[NH:48][C:49]1[CH:54]=[CH:53][CH:52]=[C:51](CN2C=CC(N)=N2)[CH:50]=1)([CH3:45])([CH3:44])[CH3:43]>C(Cl)Cl>[C:42]([O:46][C:47](=[O:62])[NH:48][C:49]1[CH:50]=[CH:51][CH:52]=[C:53]([CH2:21][N:18]2[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]3[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=3)[CH2:22][CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27]3)=[N:17]2)[CH:54]=1)([CH3:45])([CH3:43])[CH3:44]

Komponenten

6

Edukt 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazoleHCID 67190890[3-(3-Amino-pyrazol-1-ylmethyl)-phenyl]-carbamic acid tert-butyl ester

Produkt 1

HCID 67190452HCID 67190452, VerbindungAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 500 mg, 1.52 mmol) was suspended in methylene chloride (7.6 mL) and a 2.0 M solution of oxalyl chloride in methylene chloride (760 μL, 1.52 mmol) was added and the reaction stirred at 25° C. for 10 min. The solution was chilled to 0° C. and 2,6-lutidine (354 μL, 3.04 mmol) was added. The reaction continued to stir at 0° C. for 15 min. [3-(3-Amino-pyrazol-1-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (437 mg, 1.52 mmol) was dissolved in methylene chloride (7 mL) and added dropwise to the reaction. The ice bath was removed and the reaction continued to stir at 25° C. for 30 min. The reaction was diluted with ethyl acetate (300 mL), washed with water (2×50 mL), saturated aqueous brine solution (20 mL), dried over magnesium sulfate and concentrated in vacuo to a yellow foam. Purification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 5% ethyl acetate/methylene chloride to 15% ethyl acetate/methylene chloride) afforded (3-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-phenyl)-carbamic acid tert-butyl ester (539 mg 59%) as a pale pink powder: ESI-LRMS m/e calcd for C30H37ClN4O5S [M+] 600.22, found 601.50 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.23 (m, 2H, CH2), 1.45-1.93 (m, 8H, 4×CH2), 1.51 (s, 9H, 3×CH3), 2.15-2.30 (m, 1H, CH), 3.26 (s, 3H, SO2CH3), 3.54 (t, J=7.8 Hz, 1H, CH), 5.11 (s, 2H, NCH2), 6.49 (brs, 1H, NH), 6.71 (d, J=2.5 Hz, 1H, Ar), 6.82 (m, 1H, Ar), 7.19-7.25 (m, 2H, Ar), 7.26-7.29 (brs, 1H, Ar), 7.31 (d, J=2.5 Hz, 1H, Ar), 7.45 (dd, Jo=8.2, Jm=1.6 Hz, 1H, Ar), 7.59 (d, Jm=1.6 Hz, 1H, Ar), 8.08 (d, Jo=8.2 Hz. 1H, Ar), 8.17 (brs, 1H, NH).

Aufarbeitung

  1. temperatureThe solution was chilled to 0° C.
  2. additionadded dropwise to the reaction
  3. customThe ice bath was removed
  4. stirringto stir at 25° C. for 30 min
  5. additionThe reaction was diluted with ethyl acetate (300 mL)
  6. washwashed with water (2×50 mL), saturated aqueous brine solution (20 mL)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo to a yellow foam
  9. customPurification by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 5% ethyl acetate/methylene chloride to 15% ethyl acetate/methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-1d07f798cff94a34babe7c8465617383
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935699B2

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