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Tert-butyl 4-{5-[2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]pyridin-2-yl}piperazine-1-carboxylate → 8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-[6-(piperazin-1-yl)pyridin-3-yl]-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one

HRID 577522
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HRID 577522 반응식
C([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:49])[C:20]([O:45][CH:46]([CH3:48])[CH3:47])=[CH:21][C:22]=3[C:26]3[CH:27]=[CH:28][C:29]([N:32]4[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]4)=[N:30][CH:31]=3)[C:17]2=[O:50])=[C:13]([CH3:51])[CH:12]=[C:11]([CH3:52])[N:10]=1)C1C=CC=CC=1>C(O)(C(F)(F)F)=O>[Cl:49][C:19]1[C:20]([O:45][CH:46]([CH3:48])[CH3:47])=[CH:21][C:22]([C:26]2[CH:31]=[N:30][C:29]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)=[CH:28][CH:27]=2)=[C:23]2[C:18]=1[C:17](=[O:50])[N:16]([CH2:15][C:14]1[C:9](=[O:8])[NH:10][C:11]([CH3:52])=[CH:12][C:13]=1[CH3:51])[CH2:25][CH2:24]2
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참가 물질

3

반응물 1

HCID 86723748Tert-butyl 4-{5-[2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]pyridin-2-yl}piperazine-1-carboxylate

생성물 1

HCID 867237498-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-[6-(piperazin-1-yl)pyridin-3-yl]-7-(propan-2-yloxy)-3,4-dihydroisoquinolin-1(2H)-one수율 15%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

실험 절차

A mixture of tert-butyl 4-{5-[2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinolin-5-yl]pyridin-2-yl}piperazine-1-carboxylate (77f, 46 mg, 0.063 mmol) in TFA (2 mL) was stirred at room temperature for 3 hours. After concentrating volatiles under vacuum, the resulting residue was partitioned between ethyl acetate (30 mL) and sodium bicarbonate (30 mL). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (1×30 mL). The combined organic phases were dried over sodium sulfate, concentrated under vacuum, and purified by prep HPLC to give the title compound (Example 77, 5.0 mg, 15% yield) as a solid. 1H NMR (400 MHz, methanol-d4) δ 8.09 (d, J=2.27 Hz, 1H), 7.56 (dd, J=8.59, 2.53 Hz, 1H), 7.09 (s, 1H), 6.88 (d, J=8.84 Hz, 1H), 6.10 (s, 1H), 4.77 (s, 2H), 4.60-4.70 (m, 1H), 3.55-3.63 (m, 4H), 3.35 (t, J=6.06 Hz, 2H), 2.92-3.02 (m, 4H), 2.75 (t, J=6.06 Hz, 2H), 2.30 (s, 3H), 2.24 (s, 3H), 1.36 (d, J=5.81 Hz, 6H); MS 536.3 [M+H].

후처리

  1. concentrationAfter concentrating volatiles under vacuum
  2. customthe resulting residue was partitioned between ethyl acetate (30 mL) and sodium bicarbonate (30 mL)
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (1×30 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. custompurified by prep HPLC

출처 및 근거

ORD 기록
ord-5e32ec04fd7243dcbbb1b720c114b01e
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09040515B2

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