Triethylamine → HCID 117974245, compound

HRID 1776119Notes

Reaction equation

HRID 1776119 reaction equation
[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:14]([CH3:15])[O:13][C:12](=[O:16])[C@@H:11]([NH:17][C:18](=[O:28])[C:19]3[C:24]([OH:25])=[C:23]([O:26][CH3:27])[CH:22]=[CH:21][N:20]=3)[CH2:10][CH2:9][CH2:8][C@@H:7]2[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[CH2:3][CH2:2]1.CCN(CC)CC.[CH3:45][O:46][CH2:47][CH2:48][C:49](Cl)=[O:50]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:45][O:46][CH2:47][CH2:48][C:49]([O:25][C:24]1[C:19]([C:18](=[O:28])[NH:17][C@H:11]2[CH2:10][CH2:9][CH2:8][C@H:7]([CH2:29][C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)[C@@H:6]([O:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)[C@H:14]([CH3:15])[O:13][C:12]2=[O:16])=[N:20][CH:21]=[CH:22][C:23]=1[O:26][CH3:27])=[O:50]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27597283-Methoxypropanoyl chlorideHCID 117974603HCID 117974603, compound

Product 1

HCID 117974245HCID 117974245, compoundYield 78.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a 4 mL vial were added N-((3S,7R,8R,9S)-8-(cyclopropylmethoxy)-7-(4-methoxybenzyl)-9-methyl-2-oxooxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (85 mg, 0.166 mmol), CH2Cl2 (1 mL) and NEt3 (0.069 mL, 0.497 mmol), 3-methoxypropanoyl chloride (30.5 mg, 0.249 mmol), and DMAP (3 mg, 0.02 mmol), and the resulting light yellow solution was stirred at room temperature overnight. The reaction mixture was concentrated and purified by column chromatography on SiO2 (0→100% EtOAc/hexanes) to provide the title compound as a colorless semi-solid (77.8 mg, 78%): IR (neat) 3381, 2936, 1769, 1742, 1678, 1511, 1246, 1111 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=7.3 Hz, 1H), 8.31 (d, J=5.4 Hz, 1H), 7.09 (d, J=8.6 Hz, 2H), 6.98 (d, J=5.5 Hz, 1H), 6.83 (d, J=8.6 Hz, 2H), 4.91 (dq, J=9.1, 6.4 Hz, 1H), 4.55 (ddd, J=10.9, 8.4, 7.0 Hz, 1H), 3.88 (s, 3H), 3.81 (t, J=6.6 Hz, 2H), 3.78 (s, 3H), 3.57 (dd, J=9.7, 7.0 Hz, 1H), 3.44 (dd, J=9.7, 6.8 Hz, 1H), 3.41 (s, 3H), 3.15 (t, J=9.0 Hz, 1H), 3.07 (dd, J=13.4, 3.3 Hz, 1H), 2.98 (t, J=6.6 Hz, 2H), 2.35-2.20 (m, 2H), 1.87-1.77 (m, 1H), 1.61-1.47 (m, 2H), 1.48-1.37 (m, 1H), 1.45 (d, J=6.4 Hz, 3H), 1.22-1.05 (m, 2H), 0.90-0.79 (m, 1H), 0.63-0.49 (m, 2H), 0.29-0.14 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 172.61, 169.39, 162.32, 159.40, 157.82, 146.76, 141.45, 137.29, 132.66, 129.73, 113.77, 109.78, 83.79, 78.71, 75.22, 67.58, 58.78, 56.30, 55.22, 51.47, 46.17, 35.92, 34.62, 33.89, 26.55, 18.73, 18.08, 11.18, 3.16, 3.00; HRMS-ESI (m/z) ([M]+) calcd for C32H42N2O9, 598.2890; found, 598.2914.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by column chromatography on SiO2 (0→100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e1ed0d7b98674433b99e742b2742d296
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

Loading…