Hydrochloric Acid → HCID 71817397, compound

HRID 2276066Notes

Reaction equation

HRID 2276066 reaction equation
[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:14](=[O:24])[O:13][CH2:12][C@H:11]([NH:25]C(OC(C)(C)C)=O)[C:10](=[O:33])[O:9][C@H:8]1[CH3:34])(=[O:5])[CH:2]([CH3:4])[CH3:3].Cl.[OH:36][C:37]1[C:38]([C:45]([OH:47])=O)=[N:39][CH:40]=[CH:41][C:42]=1[O:43][CH3:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CCOC(C)=O>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[C:14](=[O:24])[O:13][CH2:12][C@H:11]([NH:25][C:45](=[O:47])[C:38]2[C:37]([OH:36])=[C:42]([O:43][CH3:44])[CH:41]=[CH:40][N:39]=2)[C:10](=[O:33])[O:9][C@H:8]1[CH3:34])(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 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 86701265HCID 86701265, compound

Product 1

HCID 71817397HCID 71817397, compoundYield 43.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
22 °C

Procedure

To a solution of (3S,6S,7R,8R)-8-(2-tert-butoxy-2-oxoethyl)-3-(tert-butoxycarbonylamino)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (130 mg, 0.267 mmol) in EtOAc (3 mL) was added 1M HCl in EtOAc and the solution was stirred at room temperature (about 22° C.) for 6 h. The solvent was evaporated and the residue was dissolved in CH2Cl2 (1.5 mL). To this solution was added 3-hydroxy-4-methoxypicolinic acid (58 mg, 0.345 mmol), HATU (139 mg, 0.367 mmol) and N-methylmorpholine (120 mL, 1.09 mmol), sequentially. The reaction was allowed to stir at ambient temperature for 12 h and then loaded directly onto a SiO2 column and purified by flash chromatography (hexanes/EtOAc gradient) to give the title compound (62 mg, 43%) as a white solid: mp 192-194° C.; 1H NMR (400 MHz, CDCl3) δ 11.79 (d, J=0.5 Hz, 1H), 8.63 (d, J=8.3 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 6.89 (d, J=5.1 Hz, 1H), 5.45 (s, 1H), 5.21 (dd, J=15.5, 8.3 Hz, 1H), 5.12-5.01 (m, 1H), 5.01-4.87 (m, 1H), 3.95 (s, 3H), 3.80 (d, J=25.0 Hz, 1H), 2.98 (ddd, J=11.8, 9.9, 3.2 Hz, 1H), 2.86-2.74 (m, 1H), 2.62 (dt, J=14.0, 7.0 Hz, 1H), 2.35-2.23 (m, 1H), 1.41 (s, 9H), 1.30 (dd, J=6.2, 2.4 Hz, 3H), 1.22 (dd, J=7.0, 1.6 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 175.50, 172.00, 170.26, 169.90, 169.01, 155.45, 148.86, 140.73, 129.97, 109.74, 81.74, 74.79, 74.07, 65.03, 56.13, 49.80, 45.81, 34.93, 34.02, 27.97, 18.96, 18.84, 17.79; ESIMS m/z 539 ([M+H]+).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in CH2Cl2 (1.5 mL)
  3. stirringto stir at ambient temperature for 12 h
  4. custompurified by flash chromatography (hexanes/EtOAc gradient)

Sources & evidence

ORD record
ord-1293742f8b8249188f65a5839256e917
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

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