1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → n-(7-((2s,3r,4s,5r)-3,4-Dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2h-pyran-2-yloxy)-6-isopropoxy-8-methyl-2-oxo-2h-chromen-3-yl)-1h-indole-2-carboxamide

HRID 1511438노트

반응식

HRID 1511438 반응식
[CH:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([CH3:30])[C:14]=1[O:15][C@H:16]1[C@@H:21]3[O:22]C(=O)[O:24][C@@H:20]3[C@@H:19]([O:26][CH3:27])[C:18]([CH3:29])([CH3:28])[O:17]1)[O:11][C:10](=[O:31])[C:9]([NH:32][C:33](=O)[O:34]CC1C=CC=CC=1)=[CH:8]2)([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.[NH:54]1[C:62]2[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=2)[CH:56]=[C:55]1C(O)=O.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(Cl)Cl.C(N(CC)CC)C>[OH:22][C@@H:21]1[C@H:20]([OH:24])[C@@H:19]([O:26][CH3:27])[C:18]([CH3:29])([CH3:28])[O:17][C@H:16]1[O:15][C:14]1[C:13]([CH3:30])=[C:12]2[C:7]([CH:8]=[C:9]([NH:32][C:33]([C:55]3[NH:54][C:62]4[C:57]([CH:56]=3)=[CH:58][CH:59]=[CH:60][CH:61]=4)=[O:34])[C:10](=[O:31])[O:11]2)=[CH:6][C:5]=1[O:4][CH:1]([CH3:2])[CH3:3]

참가 물질

11

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 19660Carbonate IonHCID 72899Indole-2-carboxylic acidHCID 25140398Benzyl 6-isopropoxy-7-((3aR,4S,7R,7aR)-7-methoxy-6,6-dimethyl-2-oxotetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran-4-yloxy)-8-methyl-2-oxo-2H-chromen-3-ylcarbamate

생성물 1

HCID 25140679n-(7-((2s,3r,4s,5r)-3,4-Dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2h-pyran-2-yloxy)-6-isopropoxy-8-methyl-2-oxo-2h-chromen-3-yl)-1h-indole-2-carboxamide수율 32.1%

시약·촉매·용매 6

HCID 23938Palladium촉매HCID 887Methanol용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매HCID 21875418Pyridine methylene chloride용매

실험 절차

Palladium on carbon (10%, 4 mg) was added to 25c (19.0 mg, 0.033 mmol) in anhydrous THF (220 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 (14.5 mg, 99%). EDCI (15.6 mg, 0.081 mmol) and 1H-indole-2-carboxylic acid (10.5 mg, 0.065 mmol) was added to the amine (14.5 mg, 0.033 mmol) in 30% pyridine/CH2Cl2 (1.00 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 (10.0 mg, 50%). Triethylamine (150 μL) was added to the carbonate (10.0 mg, 0.017 mmol) in MeOH (2.5 mL) and CH2Cl2 (2.50 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 10:1 CH2Cl2:Acetone) to afford 26k as a colorless amorphous solid (6.00 mg, 46%, 23% over 3 steps): 1H NMR (CDCl3, 500 MHz) 8.16 (s, 1H), 7.52 (s, 1H), 7.34-7.30 (m, 5H), 6.75 (s, 1H), 4.93 (d, J=5.0 Hz, 1H), 4.56-4.51 (m, 1H), 4.23 (t, J=4.0 Hz, 1H), 3.98-3.96 (m, 1H), 3.76 (s, 1H), 3.43 (s, 3H), 3.06 (d, J=4.3 Hz, 1H), 2.65 (s, 1H), 2.38 (s, 3H), 1.33 (dd, J=11.2, 6.1 Hz, 6H), 1.29 (s, 3H), 1.27 (s, 3H); 13C NMR (CDCl3, 125 MHz) 157.6, 152.1, 146.6, 146.0, 142.1, 134.5, 127.7, 127.5, 127.2, 122.2, 121.3 (2C), 120.2 (2C), 115.0 (2C), 108.1 (2C), 101.2, 81.6, 71.2, 68.9, 68.1, 66.5, 59.0, 24.8, 23.6, 20.8 (2C), 9.1; IR (film) νmax cm−1 3406, 2930, 2375, 1705, 1522, 1394, 1229, 1205, 1111, 1078, 1049, 933, 793, 739, 698; HRMS (ESI+) m/z: [M+Na]+ calcd for C30H34N2O9, 589.2162; found, 589.2111.

후처리

  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 (14.5 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 (10.0 mg, 50%)
  10. waitAfter 12 hours
  11. concentrationthe solvent was concentrated
  12. customthe residue purified via column chromatography (SiO2, 10:1 CH2Cl2:Acetone)

출처 및 근거

ORD 기록
ord-422a241b1a514ef5abccb30b4e77451d
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08212012B2

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