1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(7-((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yloxy)-2-oxo-8-phenyl-2H-chromen-3-yl)-3',6-dimethoxybiphenyl-3-carboxamide

HRID 1511242ノート

反応式

HRID 1511242 の反応式
[CH3:1][O:2][C@H:3]1[C:8]([CH3:10])([CH3:9])[O:7][C@@H:6]([O:11][C:12]2[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:20]3[C:15]([CH:16]=[C:17]([NH:29][C:30](=[O:39])OCC4C=CC=CC=4)[C:18](=[O:28])[O:19]3)=[CH:14][CH:13]=2)[C@@H:5]2[O:40]C(=O)[O:42][C@H:4]12.CCN=C=NCCCN(C)C.[CH3:55][O:56][C:57]1[CH:58]=[C:59]([C:63]2[C:68]([O:69][CH3:70])=[CH:67][CH:66]=[C:65](C(O)=O)[CH:64]=2)[CH:60]=[CH:61][CH:62]=1.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(Cl)Cl.C(N(CC)CC)C>[OH:40][C@@H:5]1[C@H:4]([OH:42])[C@@H:3]([O:2][CH3:1])[C:8]([CH3:10])([CH3:9])[O:7][C@H:6]1[O:11][C:12]1[C:21]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[C:20]2[C:15]([CH:16]=[C:17]([NH:29][C:30]([C:65]3[CH:64]=[C:63]([C:59]4[CH:60]=[CH:61][CH:62]=[C:57]([O:56][CH3:55])[CH:58]=4)[C:68]([O:69][CH3:70])=[CH:67][CH:66]=3)=[O:39])[C:18](=[O:28])[O:19]2)=[CH:14][CH:13]=1

参加物

11

反応物 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 25138941Benzyl 7-((3aR,4R,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxotetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-2-oxo-8-phenyl-2H-chromen-3-ylcarbamateHCID 549124263',6-Dimethoxy-(1,1'-biphenyl)-3-carboxylic acid

生成物 1

HCID 25139815N-(7-((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yloxy)-2-oxo-8-phenyl-2H-chromen-3-yl)-3',6-dimethoxybiphenyl-3-carboxamide収率 10.1%

試薬・触媒・溶媒 6

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 21875418Pyridine methylene chloride溶媒

実験手順

Palladium on carbon (10%, 14 mg) was added to 25f (68.0 mg, 0.12 mmol) in anhydrous THF (800 μL) and the solution was placed under an atmosphere of H2. After 12 hours, the solution was filtered through SiO2 (1:1 CH2Cl2:Acetone) and the eluent was concentrated to afford a yellow solid, which was used without further purification (52.0 mg, 99%). EDCI (18.5 mg, 0.096 mmol) and 3′,6-dimethoxybiphenyl-3-carboxylic acid (19.9 mg, 0.077 mmol) were added to the amine (17.5 mg, 0.039 mmol) in 30% pyridine/CH2Cl2 (1.10 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford a colorless solid, which was used without further purification (14.0 mg, 52%). Triethylamine (150 μL) was added to the carbonate (14.0 mg, 0.020 mmol) in MeOH (1.5 mL) and CH2Cl2 (1.5 mL). After 48 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26f as a colorless amorphous solid (5.20 mg, 39%, 20% over 3 steps): 1H NMR (CD2Cl2, 500 MHz) 8.85 (s, 1H), 8.65 (s, 1H), 7.92 (d, J=2.4 Hz, 1H), 7.90 (d, J=2.4 Hz, 1H), 7.86 (d, J=2.4 Hz, 1H), 7.57-7.43 (m, 3H), 7.36-7.33 (m, 4H), 7.11-7.06 (m, 3H), 6.92 (d, J=0.8 Hz, 1H), 5.52 (d, J=2.4 Hz, 1H), 4.08 (q, J=7.2, Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.74 (dd, J=9.0, 3.5 Hz, 1H), 3.50 (s, 3H), 3.23 (d, J=9.0 Hz, 1H), 2.12 (s, 1H), 2.00 (s, 1H), 1.33 (s, 3H), 1.04 (s, 3H); 13C NMR (CD2Cl2, 125 MHz) δ 164.5, 159.0 (2C), 158.6, 158.1, 154.4, 147.2, 138.0 (2C), 130.7, 130.1, 129.7, 129.1, 128.7, 128.3, 127.4, 127.2, 127.0, 127.0, 125.2, 122.6, 121.6, 121.1, 118.6, 114.5, 113.8, 112.1, 111.3, 110.2, 97.5, 70.1 (2C), 67.4, 60.8, 55.0, 54.5, 21.9, 21.6; IR (film) νmax 3402, 2932, 2359, 2341, 1713, 1603, 1524, 1500, 1367, 1267, 1086, 1040, 964, 750 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C38H37NO10, 668.2496. found, 668.2485.

後処理

  1. filtrationthe solution was filtered through SiO2 (1:1 CH2Cl2:Acetone)
  2. concentrationthe eluent was concentrated
  3. customto afford a yellow solid, which
  4. customwas used without further purification (52.0 mg, 99%)
  5. waitAfter 12 hours
  6. concentrationthe solvent was concentrated
  7. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)
  8. customto afford a colorless solid, which
  9. customwas used without further purification (14.0 mg, 52%)
  10. waitAfter 48 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

出典と根拠

ORDレコード
ord-ee7a8e01e03c4dbca960283a3d6e2bb6
出典データセット
uspto-grants-2012_07
特許番号
US08212011B2

反応ノート

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