Diisopropylethylamine → 4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide

HRID 1391478

Reaktionsgleichung

Reaktionsgleichung von HRID 1391478
[CH:1]1[C:5]2[C:6]([Cl:10])=[N:7][CH:8]=[N:9][C:4]=2[NH:3][CH:2]=1.ClC(Cl)(O[C:15](=[O:21])OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[NH2:32][C:33]1[CH:34]=[C:35]([NH:40][C:41](=[O:58])[C:42]2[CH:47]=[C:46]([C:48]([F:51])([F:50])[F:49])[CH:45]=[C:44]([N:52]3[CH:56]=[C:55]([CH3:57])[N:54]=[CH:53]3)[CH:43]=2)[CH:36]=[CH:37][C:38]=1[CH3:39]>C1COCC1>[CH3:39][C:38]1[CH:37]=[CH:36][C:35]([NH:40][C:41](=[O:58])[C:42]2[CH:47]=[C:46]([C:48]([F:49])([F:50])[F:51])[CH:45]=[C:44]([N:52]3[CH:56]=[C:55]([CH3:57])[N:54]=[CH:53]3)[CH:43]=2)=[CH:34][C:33]=1[NH:32][C:15]([N:3]1[C:4]2[N:9]=[CH:8][N:7]=[C:6]([Cl:10])[C:5]=2[CH:1]=[CH:2]1)=[O:21]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 68975748n-(3-Amino-4-methyl-phenyl)-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide

Produkt 1

HCID 596739784-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amideAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

6-Chloro-7-deazapurine (3.9 g, 25.5 mmol), triphosgene (3.80 g, 12.8 mmol), and DIEA (8.9 mL, 51 mmol) are stirred in THF (100 mL) at 0° C. for 3 hours. The THF is removed by evaporation and the residue is dissolved in THF (100 mL). The solution is mixed with N-(3-amino-4-methyl-phenyl)-3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzamide (3.5 g, 9.3 mmol) and shaken at room temperature for 18 hours. The solvent is evaporated and the residue is purified by silica gel column chromatography (2% MeOH in CH2Cl2) to obtain 4-chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide (3.4 g, yield 65%). 1H NMR (400 MHz, DMSO-d6) δ 11.07 (s, 1H), 10.71 (s, 1H), 9.62 (s, 1H), 8.99 (s, 1H), 8.62 (s, 1H), 8.55 (s, 1H), 8.46 (d, J=4.0 Hz, 1H), 8.24 (d, J=4.0 Hz, 1H), 8.18 (s, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 6.96 (d, J=4.0 Hz, 1H), 2.47 (s, 3H), 2.37 (s, 3H); ESIMS m/z 554.1 (M++1).

Aufarbeitung

  1. customThe THF is removed by evaporation
  2. dissolutionthe residue is dissolved in THF (100 mL)
  3. customThe solvent is evaporated
  4. customthe residue is purified by silica gel column chromatography (2% MeOH in CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-a57a1620a23f470796431e577cff06e9
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07338957B2

Verknüpfte Notizen

Wird geladen…