1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57590616, Verbindung

HRID 503716

Reaktionsgleichung

Reaktionsgleichung von HRID 503716
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([NH2:28])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH:29]1N=CN(C(N2C=NC=C2)=S)C=1.[F:41][C:42]([F:51])([F:50])[CH2:43][NH:44][CH2:45][CH:46]([OH:49])[CH2:47][OH:48].CCN=C=NCCCN(C)C.NC(N)=S>CN(C1C=CN=CC=1)C.O.ClCCCl.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([N:28]=[C:29]4[N:44]([CH2:43][C:42]([F:50])([F:51])[F:41])[CH2:45][CH:46]([CH2:47][OH:48])[O:49]4)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Komponenten

10

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 802641,1'-ThiocarbonyldiimidazoleHCID 2723790ThioureaHCID 53630477Allitinib metabolite M62×HCID 60632717HCID 60632717, Verbindung

Produkt 1

HCID 57590616HCID 57590616, VerbindungAusbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 111,2-DichloroethaneLösungsmittel3×HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

[2-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-ylimino}-3-(2,2,2-trifluoro-ethyl)-oxazolidin-5-yl]-methanol is prepared from N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine. 1,1-Thiocarbonyldiimidazole (55 mg, 0.28 mmol) is added to a solution of N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine (100 mg, 0.253 mmol) in 1:1 THF:DCE (1 ml). After 30 min, a 1:1 THF:DCE (1 ml) solution of 3-(2,2,2-trifluoro-ethylamino)-propane-1,2-diol (88 mg, 0.51 mmol) is added. After 16 h, the reaction mixture is concentrated and the resulting solid is suspended in Et2O and filtered. EDCI (110 mg, 0.560 mmol) and catalytic DMAP is added to a suspension of the solid thiourea in 1:1 THF:DCE (4 ml). After 6 h, an additional 200 mg EDCI is added and the reaction mixture is heated to 70° C. After 16 h, the reaction mixture is cooled to room temperature and diluted with water. The aqueous layer is extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated. Purification on a silica gel column (EtOAc) yields the desired product as a yellow solid (10 mg, 7%). MS ESI (+) m/z 576.2, 578.2 (M+1) detected; 1H NMR (400 MHz, DMSO-d6) δ 9.56 (s, 1H), 8.47 (s, 1H), 8.08 (d, 1H), 7.94 (s, 1H), 7.77 (m, 1H), 7.62 (m, 2H), 7.47 (m, 1H), 7.32 (m, 2H), 7.24 (d, 1H) 7.19 (m, 1H), 5.25 (s, 2H), 5.19 (t, 1H), 4.77 (br, 1H), 3.77 (m, 1H), 3.66 (m, 1H), 3.55 (m, 2H), 2.97 (m, 2H).

Aufarbeitung

  1. waitAfter 16 h
  2. concentrationthe reaction mixture is concentrated
  3. filtrationfiltered
  4. waitAfter 6 h
  5. waitAfter 16 h
  6. temperaturethe reaction mixture is cooled to room temperature
  7. extractionThe aqueous layer is extracted with EtOAc
  8. dry with materialThe combined organic extracts are dried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification on a silica gel column (EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-f9d020b97680454b8c63c92e6835a507
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07777032B2

Verknüpfte Notizen

Wird geladen…