4-Methylmorpholine → HCID 86701325, compound

HRID 2283019Notes

Reaction equation

HRID 2283019 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-0143af6c27c64d4099b1c40d06b94414
Source dataset
uspto-grants-2015_09
Patent number
US09144239B2

Reaction notes

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