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Lithium hydroxide, monohydrate → 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60165
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HRID 60165 반응식
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH:24]([CH3:26])[CH3:25])[N:16]=[CH:17][C:10]=2[N:9]([CH3:35])[C:8]1=[O:36])=O.O[Li].O>C1COCC1.O.CC(=O)OCC>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:36])[N:9]([CH3:35])[C:10]=3[CH:17]=[N:16][C:15]=2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH:24]([CH3:26])[CH3:25])=[CH:33][CH:32]=1
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반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 1188753133-(5-(4-chlorobenzyl)-6-(2-isopropylphenyl)-1-methyl-2,4-dioxo-1,2-dihydro pyrido[3,4-d]pyrimidin-3(4H)-yl)propyl formate

생성물 1

HCID 1188750245-(4-chlorobenzyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione수율 36.4%

시약·촉매·용매 3

HCID 962Water용매
HCID 8028
Tetrahydrofuran
용매
HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 3-(5-(4-chlorobenzyl)-6-(2-isopropylphenyl)-1-methyl-2,4-dioxo-1,2-dihydro pyrido[3,4-d]pyrimidin-3(4H)-yl)propyl formate (7 mg, 0.0138 mmol) in THF (0.5 mL) and water (0.5 mL) was added LiOH.H2O (1.2 mg, 0.0277 mmol). The reaction was stirred at RT for 30 min then diluted with EA (5 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:2) to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (2.4 mg, 36.4% yield) as a white solid. 1H NMR (CDCl3) δ: 8.79 (s, 1H), 7.38 (d, J=3.8 Hz, 2H), 7.20-7.12 (m, 1H), 7.10 (t, J=8.4 Hz, 2H), 6.97 (d, J=7.5 Hz, 1H), 6.71 (d, J=8.4 Hz, 2H), 5.34 (s, 1H), 4.79 (d, J=14.9 Hz, 1H), 4.19 (t, J=6.1 Hz, 2H), 3.76 (s, 3H), 3.48 (d, J=6.1 Hz, 2H), 2.77 (s, 1H), 2.01 (d, J=5.9 Hz, 1H), 1.92-1.80 (m, 2H), 1.10 (d, J=6.8 Hz, 3H), 1.02 (d, J=6.9 Hz, 3H). LCMS: MH+ 478 and TR=4.088 min.

후처리

  1. washThe organic layer was washed with brine (10 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by Prep TLC
  5. washeluted with PE/EA (1:2)

출처 및 근거

ORD 기록
ord-030518ecb52f420396c2e6e0d6eed155
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09440973B2

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