Lithium Hydroxide → N-[3-(3-{2-[(2-Amino-2,3-dihydro-1H-inden-5-yl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamide

HRID 1157623Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157623
FC(F)(F)C([NH:5][CH:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]4[C:23]([C:31]5[CH:36]=[CH:35][CH:34]=[C:33]([NH:37][C:38](=[O:45])[CH2:39][C:40]6[S:41][CH:42]=[CH:43][CH:44]=6)[CH:32]=5)=[N:24][N:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=45)[CH:19]=[CH:18][N:17]=3)[CH:12]=2)[CH2:7]1)=O.[Li+].[OH-]>CO>[NH2:5][CH:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:15][C:16]3[N:21]=[C:20]([C:22]4[C:23]([C:31]5[CH:32]=[C:33]([NH:37][C:38](=[O:45])[CH2:39][C:40]6[S:41][CH:42]=[CH:43][CH:44]=6)[CH:34]=[CH:35][CH:36]=5)=[N:24][N:25]5[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=45)[CH:19]=[CH:18][N:17]=3)[CH:12]=2)[CH2:7]1

Komponenten

4

Edukt 2

HCID 3939Lithium Hydroxide2×HCID 577371772,2,2-Trifluoro-N-(5-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-2,3-dihydro-1H-inden-2-yl)acetamide

Produkt 1

HCID 57737244N-[3-(3-{2-[(2-Amino-2,3-dihydro-1H-inden-5-yl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamideAusbeute 79,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

2,2,2-Trifluoro-N-(5-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-2,3-dihydro-1H-inden-2-yl)acetamide (61 mg, 0.09 mmol) was stirred with LiOH (20 mg, 0.47 mmol) in MeOH (5 mL) at rt. After 24 h. additional LiOH (20 mg, 0.47 mmol) was added and the reaction stirred until complete conversion was indicated by LC/MS analysis. The MeOH was removed under vacuum and the residue partitioned between EtOAc and water. The organic was washed with brine and dried with MgSO4. The solvent was removed and the crude product was purified by silica gel flash column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq)) and yielded 40 mg (77%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.37 (s, 1H), 8.79 (d, J=7.0 Hz, 1H), 8.45 (d, J=8.6 Hz, 1H), 8.19 (d, J=5.3 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.62 (s, 1H), 7.46-7.32 (m, 4H), 7.24 (d, J=7.6 Hz, 1H), 7.09 (t, J=6.9 Hz, 1H), 7.01 (d, J=8.0 Hz, 1H), 6.95 (m, 1H), 6.42 (d, J=5.3 Hz, 1H), 3.85 (s, 2H), 3.65 (m, 1H), 2.94 (dd, J=15.5, 6.8 Hz, 2H), 2.47 (m, 2H), 1.83 (s, 2H). ES-LC/MS m/z=558 [M+H]+.

Aufarbeitung

  1. customThe MeOH was removed under vacuum
  2. customthe residue partitioned between EtOAc and water
  3. washThe organic was washed with brine
  4. dry with materialdried with MgSO4
  5. customThe solvent was removed
  6. customthe crude product was purified by silica gel flash column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq))

Quellen und Nachweise

ORD-Eintrag
ord-8b2d735be6a34bb784105dbc8ac8ea1a
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807673B2

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