N-(3-aminobenzyl)-2,2,2-trifluoroacetamide → 2,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}-pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamide

HRID 1157592

Reaktionsgleichung

Reaktionsgleichung von HRID 1157592
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.O1C(C2C=C(N[C:28]3[N:33]=[C:32]([C:34]4[C:35]([C:43]5[CH:44]=[C:45]([NH:49][C:50](=[O:57])[CH2:51][C:52]6[S:53][CH:54]=[CH:55][CH:56]=6)[CH:46]=[CH:47][CH:48]=5)=[N:36][N:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=45)[CH:31]=[CH:30][N:29]=3)C=CC=2)=CN=C1>CC(O)C.Cl.C(Cl)Cl>[F:14][C:11]([F:12])([F:13])[C:10]([NH:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:28]2[N:33]=[C:32]([C:34]3[C:35]([C:43]4[CH:48]=[CH:47][CH:46]=[C:45]([NH:49][C:50](=[O:57])[CH2:51][C:52]5[S:53][CH:54]=[CH:55][CH:56]=5)[CH:44]=4)=[N:36][N:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=34)[CH:31]=[CH:30][N:29]=2)[CH:3]=1)=[O:15]

Komponenten

6

Edukt 2

HCID 21131928N-(3-aminobenzyl)-2,2,2-trifluoroacetamideHCID 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)acetamide

Produkt 1

HCID 577372032,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}-pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamideAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidKatalysatorHCID 3776IsopropanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

A suspension of N-[(3-aminophenyl)methyl]-2,2,2-trifluoroacetamide (46 mg, 0.21 mmol) and N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (75 mg, 0.17 mmol) (see Example 2, Step B) in i-PrOH (3 mL) was acidified with 2 drops of 12 N HCl and heated in a microwave for 15 min. at 180° C. The reaction mixture was then diluted with DCM, washed with saturated aqueous NaHCO3, dried over Na2SO4, and adsorbed onto silica gel. The crude product was purified by column chromatography to generate the title compound in 67% yield. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=6.8 Hz, 1H), 8.31 (d, J=9.1 Hz, 1H), 8.22 (d, J=5.2 Hz, 1H), 7.72-7.75 (m, 2H), 7.63 (s, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.26-7.38 (m, 7H), 7.04 (s, 1H), 6.94 (m, 1H), 6.63 (d, J=5.4 Hz, 1H), 4.48 (d, J=5.7 Hz, 2H), 3.96 (s, 2H). ES-LC/MS m/z=628 [M+H]+.

Aufarbeitung

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialdried over Na2SO4
  3. customThe crude product was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-557c8ceabab04b84bf7b94a00b95b16a
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807673B2

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