Acetyl chloride → 4-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide

HRID 1391483

Reaktionsgleichung

Reaktionsgleichung von HRID 1391483
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:26])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([N:20]3[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]3)[CH:11]=2)=[CH:4][C:3]=1[NH:27][C:28]([N:30]1[C:34]2[N:35]=[CH:36][N:37]=[C:38](Cl)[C:33]=2[CH:32]=[CH:31]1)=[O:29].C(Cl)(=O)C.[OH:44][CH:45]([C:47]1[CH:48]=[C:49]([CH:51]=[CH:52][CH:53]=1)[NH2:50])[CH3:46]>C(O)CCC>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:26])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([N:20]3[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]3)[CH:11]=2)=[CH:4][C:3]=1[NH:27][C:28]([N:30]1[C:34]2[N:35]=[CH:36][N:37]=[C:38]([NH:50][C:49]3[CH:51]=[CH:52][CH:53]=[C:47]([CH:45]([OH:44])[CH3:46])[CH:48]=3)[C:33]=2[CH:32]=[CH:31]1)=[O:29]

Komponenten

5

Edukt 3

HCID 6367Acetyl chlorideHCID 2224611-(3-Aminophenyl)ethanolHCID 596739784-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide

Produkt 1

HCID 113881924-[3-(1-Hydroxy-ethyl)-phenylamino]-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 2631-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

4-Chloro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide resin (50 mg, 0.05 mmol), prepared as in reference 3, in n-butanol (2 mL) is mixed with acetyl chloride (17.8 μL, 0.25 mmol) and 3-(1-hydroxyethyl)aniline (34 mg, 0.25 mmol) and shaken at 80° C. for 24 hours. The resulting mixture is filtered and the resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes before filtering and washing with CH2Cl2 (3×2 mL), MeOH (3×2 mL). The washes are then combined together with n-butanol and concentrated. The residue is purified by preparative HPLC-MS to give 4-[3-(1-hydroxy-ethyl)-phenylamino]-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid {2-methyl-5-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-benzoylamino]-phenyl}-amide (16.6 mg, yield 51%); 1HNMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 10.68 (s, 1H), 9.85 (s, 1H), 9.62 (s, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.54 (s, 1H), 8.47 (s, 1H), 8.43 (s, 1H), 8.17 (s, 1H), 7.85 (d, J=4.1 Hz, 2H), 7.70 (s, 1H), 7.61 (dd, J=6.5, 8.2 Hz, 1H), 7.35 (d, J=2.3 Hz, 1H), 7.33 (t, J=7.8 Hz, 1H), 7.09 (s, 1H), 7.08 (d, J=6.8 Hz, 1H), 4.75 (q, J=6.4 Hz, 1H), 2.47 (s, 3H), 2.36 (s, 3H), 1.36 (d, J=6.4 Hz, 3H); ESIMS m/z 655.2 (M++1).

Aufarbeitung

  1. filtrationThe resulting mixture is filtered
  2. additionthe resin is treated with TFA/CH2Cl2/H2O (45/50/5) (600 μL) for 30 minutes
  3. filtrationbefore filtering
  4. washwashing with CH2Cl2 (3×2 mL), MeOH (3×2 mL)
  5. concentrationconcentrated
  6. customThe residue is purified by preparative HPLC-MS

Quellen und Nachweise

ORD-Eintrag
ord-a6516b3b76514903927d3ac9b4f2b8c9
Quelldatensatz
uspto-grants-2008_03
Patentnummer
US07338957B2

Verknüpfte Notizen

Wird geladen…