Hydrochloric Acid → HCID 67273441, compound

HRID 1698376Notes

Reaction equation

HRID 1698376 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([NH:14]C)[CH2:11][C@@H:10]([C:16](=[O:39])[N:17](C2CC2)[C:18]2[CH:19]=[CH:20][C:21]3[O:26][C:25]([CH3:28])([CH3:27])[C:24](=[O:29])[N:23]([CH2:30][CH2:31][CH2:32][O:33][CH3:34])[C:22]=3[CH:35]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:40]1([C:46]2([C:49]([OH:51])=O)[CH2:48][CH2:47]2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([NH:14][C:49]([C:46]2([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH2:47][CH2:48]2)=[O:51])[CH2:11][C@@H:10]([C:16](=[O:39])[NH:17][C:18]2[CH:19]=[CH:20][C:21]3[O:26][C:25]([CH3:27])([CH3:28])[C:24](=[O:29])[N:23]([CH2:30][CH2:31][CH2:32][O:33][CH3:34])[C:22]=3[CH:35]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 802061-Phenylcyclopropanecarboxylic acidHCID 181649HOAtHCID 67272425HCID 67272425, compound

Product 1

HCID 67273441HCID 67273441, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (3R,5S)-3-{Cyclopropyl-[4-(3-methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-di hydro-2H-benzo[1,4]oxazin-6-yl]-carbamoyl}-5-methylamino-piperidine-1-carboxylic acid tert-butyl ester (110 mg, 0.2 mmol) and 1-phenyl-1-cyclopropanecarboxylic acid (40 mg, 0.24 mmol) in DMF (2 mL) are added EDCI. HCl (60 mg, 0.3 mmol) and HOAt (40 mg, 0.3 mmol) at 0° C. After stirred at rt overnight, the reaction mixture is diluted with EtOAc. The mixture is washed with water and dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified by silica gel column chromatography to afford (3R,5S)-3-[4-(3-Methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylcarbamoyl]-5-[(1-phenylcyclopropanecarbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester as a white amorphous, which is treated with 4 N HCl in 1,4-dioxane (3 mL). The solution is concentrated under reduced pressure to give the title compound as a yellow powder. MS: 589 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 3.01 min.

Workup

  1. customat 0° C
  2. washThe mixture is washed with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d81ca1a6e20543cdb9eebeb7b22dea16
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

Loading…