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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
ノート
印刷プレビュー

反応式

HRID 577522 の反応式
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
参加物実験手順後処理出典と根拠反応ノート

参加物

3

反応物 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

生成物 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)-one収率 15%

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

実験手順

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].

後処理

  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

出典と根拠

ORDレコード
ord-5e32ec04fd7243dcbbb1b720c114b01e
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09040515B2

反応ノート

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