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

HRID 2272793Notes

Reaction equation

[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]([CH3:22])=[C:20]3[C:15]([CH:16]=[C:17]([NH:24]C(=O)OCC4C=CC=CC=4)[C:18](=[O:23])[O:19]3)=[CH:14][C:13]=2[O:35][CH2:36][CH2:37][CH3:38])[C@@H:5]2[O:39]C(=O)[O:41][C@H:4]12.CCN=C=NCCCN(C)C.[CH3:54][O:55][C:56]1[CH:57]=[C:58]([C:62]2[C:67]([O:68][CH3:69])=[CH:66][CH:65]=[C:64]([C:70](O)=[O:71])[CH:63]=2)[CH:59]=[CH:60][CH:61]=1.C(=O)([O-])[O-]>[Pd].C1COCC1.N1C=CC=CC=1.C(Cl)Cl.CO.C(N(CC)CC)C>[OH:39][C@@H:5]1[C@H:4]([OH:41])[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]([CH3:22])=[C:20]2[C:15]([CH:16]=[C:17]([NH:24][C:70]([C:64]3[CH:63]=[C:62]([C:58]4[CH:59]=[CH:60][CH:61]=[C:56]([O:55][CH3:54])[CH:57]=4)[C:67]([O:68][CH3:69])=[CH:66][CH:65]=3)=[O:71])[C:18](=[O:23])[O:19]2)=[CH:14][C:13]=1[O:35][CH2:36][CH2:37][CH3:38]

Participants

Procedure

Palladium on carbon (10%, 85.0 mg) was added to 25b (425 mg, 0.7283 mmol) in anhydrous THF (4.90 mL) and the solution was placed under an atmosphere of H2. After 6.5 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 (325 mg, 99%). EDCI (116 mg, 0.60 mmol) and 3′,6-dimethoxybiphenyl-3-carboxylic acid (125 mg, 0.4821 mmol) were added to the amine (108 mg, 0.2410 mmol) in 30% pyridine/CH2Cl2 (6.70 mL). After 12 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 3:1 Hexane:Ether→20:1 CH2Cl2:Acetone) to afford a colorless solid, which was used without further purification (51.0 mg, 31%). Triethylamine (150 μL) was added to the carbonate (51.0 mg, 0.074 mmol) in MeOH (2.50 mL). After 48 hours, the solvent was concentrated and the residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone) to afford 26b as a colorless amorphous solid (22.8 mg, 47%, 14% over 3 steps): 1H NMR (CD2Cl2, 400 MHz) δ 8.79 (s, 1H), 8.78 (s, 1H), 7.96 (dd, J=8.6, 2.4 Hz, 1H), 7.91 (d, J=2.4 Hz, 1H), 7.39 (t, J=7.9 Hz, 1H), 7.16-7.11 (m, 2H), 6.97-6.94 (m, 2H), 5.97 (s, 1H), 5.14 (d, J=6.5 Hz, 1H), 4.31 (t, J=3.5 Hz, 1H), 4.12-4.06 (m, 2H), 4.03 (dd, J=6.8, 1.8 Hz, 1H), 3.93 (s, 3H), 3.88 (s, 3H), 3.65 (s, 1H), 3.53 (s, 3H), 3.17 (d, J=4.8 Hz, 1H), 2.80 (s, 1H), 2.48 (s, 3H), 1.95-1.90 (m, 2H), 1.37 (s, 3H), 1.35 (s, 3H), 1.11 (t, J=7.4 Hz, 3H); 13C NMR (CDCl3, 125 MHz) δ 165.0, 164.6, 158.8, 158.3, 147.7, 145.7, 142.3, 137.8, 137.5, 131.3, 129.0, 128.2, 127.2, 124.9, 122.3, 121.2, 121.0, 115.111, 114.2, 112.1, 110.0, 106.2, 101.1, 81.7, 70.0, 69.0, 68.0, 64.8, 59.1, 54.9, 54.3, 24.7, 24.0, 21.3, 9.5, 9.1; IR (film) νmax 3398, 3196, 2964, 2935, 2359, 2330, 1705, 1580, 1526, 1504, 1381, 1242, 1124, 1094, 939, 808, 760, 735 cm−1; HRMS (ESI+) m/z: [M+H]+ calcd for C36H41NO11, 664.2758. found, 664.2754.

Workup

filtrationthe solution was filtered through SiO2 (1:1 CH2Cl2:Acetone)
concentrationthe eluent was concentrated
customto afford a yellow solid, which
customwas used without further purification (325 mg, 99%)
waitAfter 12 hours
concentrationthe solvent was concentrated
customthe residue purified via column chromatography (SiO2, 3:1 Hexane:Ether→20:1 CH2Cl2:Acetone)
customto afford a colorless solid, which
customwas used without further purification (51.0 mg, 31%)
waitAfter 48 hours
concentrationthe solvent was concentrated
customthe residue purified via column chromatography (SiO2, 40:1 CH2Cl2:Acetone)

Sources & evidence

ORD record: ord-5febeff61012420f9adf9efbebbe121d
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120774B2

Reaction notes

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Reaction equation

Participants

Reactant 4

Product 1

Reagents, catalysts & solvents 5

Procedure

Workup

Sources & evidence

Reaction notes