Tris(hydroxymethyl)aminomethane → N-{3-[3-(2-{[3-(1,3-Oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

HRID 1157535

Reaktionsgleichung

Reaktionsgleichung von HRID 1157535
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]5[O:34][CH:33]=[N:32][CH:31]=5)[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[S:35]1[CH:39]=[CH:38][CH:37]=[C:36]1[CH2:40][C:41](Cl)=[O:42].C(O)C(N)(CO)CO>C1COCC1>[O:34]1[C:30]([C:26]2[CH:25]=[C:24]([NH:23][C:19]3[N:18]=[C:17]([C:16]4[C:8]([C:4]5[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH2:40][C:36]6[S:35][CH:39]=[CH:38][CH:37]=6)[CH:7]=[CH:6][CH:5]=5)=[N:9][N:10]5[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=45)[CH:22]=[CH:21][N:20]=3)[CH:29]=[CH:28][CH:27]=2)=[CH:31][N:32]=[CH:33]1

Komponenten

5

Edukt 3

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 1623622-Thiopheneacetyl chlorideHCID 577371674-[2-(3-Aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-[3-(1,3-oxazol-5-yl)phenyl]-2-pyrimidinamine

Produkt 1

HCID 57737194N-{3-[3-(2-{[3-(1,3-Oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamideAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred solution of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-[3-(1,3-oxazol-5-yl)phenyl]-2-pyrimidinamine (100 mg, 0.22 mmol) in 1 mL THF was added 2-thiopheneacetyl chloride (40 mg, 0.25 mmol). After 15 min. LC/MS indicated the reaction was complete and several equivalents of PS-trisamine were added and the mixture was stirred for 16 h followed by addition of 25 mg of TEA. The mixture was filtered and the resin washed well with THF. The filtrate was concentrated and the crude purified by HPLC (Agilent, 50-90% gradient over 15 min.) to give the title compound (45 mg, 36% yield). 1H NMR (400 MHz, d6-DMSO) δ 10.34 (s, 1H), 9.71 (s, 1H), 8.81 (d, J=6.8 Hz, 1H), 8.49 (d, J=8.6 Hz, 1H), 8.18-8.37 (m, 3H), 7.87 (s, 1H), 7.67-7.72 (m, 2H), 7.54 (s, 1H), 7.24-7.42 (m, 6H), 7.09 (t, J=6.9 Hz, 1H), 6.93-6.95 (m, 2H), 6.49 (d, J=5.3 Hz, 1H), 3.84 (s, 2H) ppm. ES-LC/MS m/z=570 [M+H]+

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. washthe resin washed well with THF
  3. concentrationThe filtrate was concentrated
  4. customthe crude purified by HPLC (Agilent, 50-90% gradient over 15 min.)

Quellen und Nachweise

ORD-Eintrag
ord-349798a67f644183b9eebf7d9d5ff935
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807673B2

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