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Uridine → 6-{4-(4-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-6-hydroxymethyl-tetrahydro-furo(3,4-d)(1,3)dioxol-2-yl)-phenoxy}-hexanoic acid ethyl ester

HRID 1797382
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HRID 1797382 반응식
[C@@H:1]1([N:10]2[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].[CH2:18]([O:20][C:21](=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34](OC)OC)=[CH:30][CH:29]=1)[CH3:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(N(CC)CC)C>CN(C=O)C>[CH2:18]([O:20][C:21](=[O:39])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]2[O:5][CH:4]3[CH:6]([CH2:7][OH:8])[O:9][CH:1]([N:10]4[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]4=[O:12])[CH:2]3[O:3]2)=[CH:30][CH:29]=1)[CH3:19]
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참가 물질

6

반응물 4

HCID 6029UridineHCID 8471TriethylamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 695885636-(4-Dimethoxymethyl-phenoxy)-hexanoic acid ethyl ester

생성물 1

HCID 695881876-{4-(4-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-6-hydroxymethyl-tetrahydro-furo(3,4-d)(1,3)dioxol-2-yl)-phenoxy}-hexanoic acid ethyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

Uridine 5 (7, 50 g, 0.21 mol) together with 4 (70 g, 0.23 mol) was dissolved in DMF (150 mL). p-Toluenesulfonic acid monohydrate (3.8 g, 20 mmol) was added, the mixture was placed on a Buechi R-134 rotavapor and agitated under reduced pressure (70 mbar) at 50° C. for 15 h. The mixture was then neutralized with triethylamine (2.8 ml, 20 mmol) and subsequently concentrated in vacuo. The resulting residue was suspended in EtOAc (400 mL), filtered and washed with 1:1 EtOAc/H2O (400 mL), H2O (2×200 mL), 1:1 H2O/Et2O (200 mL) and Et2O (2×200 mL) to give a colorless solid as a mixture of 2 diastereomers (6, 77 g, 0.16 mol, 76%). Upon recrystallisation from EtOH/EtOAc one of the diastereomers exclusively crystallized: M.p.: 176-178° C.; 1H-NMR (400 MHz, (CD3)2SO3) δ=11.38 (s, 1H), 7.82 (d, J=8.1, 1H), 7.42 (d, J8.6, 2H), 6.95 (d, J=8.6, 2H), 5.94 (s, 1H), 5.90 (s, 1H), 5.64 (d, J=8.1, 1H), 5.10 (t, J=5.2, 1H), 4.99 (m, 1H), 4.82 (m, 1H), 4.23 (m, 1H), 4.04 (q, J=7.1, 2H), 3.97 (t, J=6.3, 2H), 3.60 (m, 2H), 2.30 (t, J=7.4, 2H), 1.71 (m, 2H), 1.58 (m, 2H), 1.41 (m, 2H), 1.16 (t, J=7.1, 3H); 13C-NMR (400 MHz, (CD3)2SO) δ=172.8, 163.2, 159.7, 150.3, 142.1, 128.4 (2C), 128.0, 114.2 (2C), 106.5, 101.7, 91.3, 86.4, 84.2, 81.6, 67.4, 61.3, 59.6, 33.4, 28.3, 25.0, 24.2, 14.1; IR (film) ν=3467, 2933, 1692, 1677, 1248, 1116, 1077, 828; HRMS (MALDI-FTMS) m/z 513.1851 (513.1849 calculated for C24H30N2O9Na (M+Na)+).

후처리

  1. concentrationsubsequently concentrated in vacuo
  2. filtrationfiltered
  3. washwashed with 1:1 EtOAc/H2O (400 mL), H2O (2×200 mL), 1:1 H2O/Et2O (200 mL) and Et2O (2×200 mL)
  4. customto give a colorless solid
  5. additionas a mixture of 2 diastereomers (6, 77 g, 0.16 mol, 76%)
  6. customUpon recrystallisation from EtOH/EtOAc one of the diastereomers
  7. customexclusively crystallized

출처 및 근거

ORD 기록
ord-a07287336a1b442ba6c7b02783fb1f00
출처 데이터셋
uspto-grants-2006_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07034147B2

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