N-Trifluoroacetylprolyl chloride → (S)-1-(2,2,2-trifluoroethanoyl)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amide

HRID 1821728Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1821728
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH3:19])=[C:6]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[N:16][CH:15]=[CH:14][N:13]=2)=[O:10])[CH:7]=1.[F:20][C:21]([F:33])([F:32])[C:22]([N:24]1[CH2:31][CH2:30][CH2:29][C@H:25]1[C:26](Cl)=[O:27])=[O:23]>N1C=CC=CC=1>[CH3:19][O:18][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:26]([C@@H:25]2[CH2:29][CH2:30][CH2:31][N:24]2[C:22](=[O:23])[C:21]([F:33])([F:20])[F:32])=[O:27])=[CH:7][C:6]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1)=[O:10]

Komponenten

4

Edukt 2

HCID 3082449N-Trifluoroacetylprolyl chlorideHCID 22046278HCID 22046278, Verbindung2×

Produkt 1

HCID 86587622(S)-1-(2,2,2-trifluoroethanoyl)-pyrrolidine-2-carboxylic acid [4-methoxy-3-(3-pyrazin-2-yl-ureido)-phenyl]-amideAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Versuchsvorschrift

A solution of 1-(5-amino-methoxyphenyl)-3-pyrazin-2-yl-urea (Compound 14, Example 4) (105 mg, 0.4 mmol) in dry pyridine (2 mL) at 0° C. was treated with a solution of N-trifluoroacetyl-(S)-prolyl chloride (0.1 M in dichloromethane, 4.5 mL, 0.45 mmol) and stirred 2 h at room temperature. The reaction was quenched with 1 N HCl (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with 1 N HCl (2×20 mL), water (20 mL), brine (20 mL), dried over sodium sulfate, and concentrated in vacuo to a beige solid (60 mg). Recrystallization from acetonitrile yielded the final solid product (30 mg, 17%). 1H NMR (300 Mhz, d6-DMSO) δ: (10.16-10.06, m, 3H), 8.90 (s, 1H), 8.36-8.30 (m, 2H), 8.25 (d, J=2.6 Hz, 1H), 7.42 (dd, J=8.8, 2.6 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 4.57 (dd, J=8.5, 4.4 Hz, 1H), 3.88 (s, 3H), 3.73 (t, J=6.5 Hz, 1H), 2.27-2.21 (m, 1H), 2.06-1.90 (m, 3H). LRMS (ESI, positive) m/e 453.1 (M+1).

Aufarbeitung

  1. customThe reaction was quenched with 1 N HCl (50 mL)
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with 1 N HCl (2×20 mL), water (20 mL), brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo to a beige solid (60 mg)
  6. customRecrystallization from acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-4ae8af0d0b274d9eb1e61769ab9976ac
Quelldatensatz
uspto-grants-2009_10
Patentnummer
US07608618B2

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