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 1157623

반응식

HRID 1157623 반응식
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

참가 물질

4

반응물 2

HCID 3939Lithium Hydroxide2회HCID 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

생성물 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)acetamide수율 79.7%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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]+.

후처리

  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))

출처 및 근거

ORD 기록
ord-8b2d735be6a34bb784105dbc8ac8ea1a
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807673B2

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