4-Methylmorpholine → HCID 86701325, compound

HRID 1627052Notes

Reaction equation

HRID 1627052 reaction equation
[NH2:1][C@H:2]1[CH2:10][O:9][CH2:8][C@H:7]([O:11][C:12]([CH3:16])([CH3:15])[CH2:13][CH3:14])[C@@H:6]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])[C@H:5]([CH3:22])[O:4][C:3]1=[O:23].[OH:24][C:25]1[C:26]([C:33](O)=[O:34])=[N:27][CH:28]=[CH:29][C:30]=1[O:31][CH3:32].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[OH:24][C:25]1[C:26]([C:33]([NH:1][C@H:2]2[CH2:10][O:9][CH2:8][C@H:7]([O:11][C:12]([CH2:13][CH3:14])([CH3:15])[CH3:16])[C@@H:6]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])[C@H:5]([CH3:22])[O:4][C:3]2=[O:23])=[O:34])=[N:27][CH:28]=[CH:29][C:30]=1[O:31][CH3:32]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110411213-Hydroxy-4-methoxypyridine-2-carboxylic acidHCID 86701326HCID 86701326, compound

Product 1

HCID 86701325HCID 86701325, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (3S,7S,8S,9S)-3-amino-7-(1,1-dimethylpropoxy)-8-isobutoxy-9-methyl-1,5-dioxonan-2-one and 3-hydroxy-4-methoxypicolinic acid (79.0 mg, 0.466 mmol) in DCM (2.0 mL) were added 4-methylmorpholine (0.205 mL, 1.86 mmol) followed by HATU (189 mg, 0.497 mmol) and the mixture was stirred at room temperature for 16 h. The reaction mixture was directly purified by flash chromatography (SiO2, hexanes/EtOAc gradient) to yield the title compound as a white solid (50.0 mg, 42%): mp 138-140° C.; IR (neat) 3370, 2926, 1750, 1650, 1529, 1243, 1085 cm−1; 1H NMR (400 MHz, CDCl3) δ 11.98 (s, 1H), 8.73 (d, J=8.0 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 6.87 (d, J=5.2 Hz, 1H), 5.08 (dq, J=9.1, 6.3 Hz, 1H), 5.00 (ddd, J=8.1, 6.1, 3.8 Hz, 1H), 4.00 (dd, J=12.1, 6.1 Hz, 1H), 3.94 (s, 3H), 3.95-3.89 (m, 2H), 3.79 (dd, J=8.6, 5.6 Hz, 1H), 3.56-3.45 (m, 2H), 3.07 (dt, J=12.6, 8.4 Hz, 2H), 1.90-1.78 (m, 1H), 1.56-1.43 (m, 2H), 1.45 (d, J=6.4 Hz, 3H), 1.15 (s, 3H), 1.14 (s, 3H), 0.93 (d, J=6.6 Hz, 3H), 0.91-0.85 (m, 6H); 13C NMR (101 MHz, CDCl3) δ 170.17, 169.09, 155.47, 148.89, 140.79, 130.47, 109.68, 85.26, 81.29, 81.18, 77.82, 75.32, 75.19, 73.37, 56.23, 53.07, 35.01, 29.10, 25.16, 25.08, 19.95, 19.60, 18.97, 9.06; HRMS-ESI (m/z) [M]+ calcd for C24H38N2O8, 482.2628; found, 482.2631.

Workup

  1. customThe reaction mixture was directly purified by flash chromatography (SiO2, hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-16410cabde3f4ac2b79e3ea9ac7cc0e9
Source dataset
uspto-grants-2014_07
Patent number
US08785479B2

Reaction notes

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