Reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][CH2:7][CH:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:51][C@H:52]([CH:57]([CH3:59])[CH3:58])[C:53]([O:55][CH3:56])=[O:54]>CN(C=O)C>[CH3:56][O:55][C:53](=[O:54])[CH:52]([NH:51][C:9](=[O:11])[CH:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][O:6][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:21][CH:20]=1)[CH:57]([CH3:59])[CH3:58]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -15 °C
Procedure
A solution of the compound obtained in step e above (22e) (816 mg, 2.27 mmol), NMM (0.55 mL, 4.922 mmol) and HOBt (521 mg, 3.864 mmol) in DMF (10 mL) was stirred at 0° C. for 10 minutes, then the reaction was cooled to −15° C., and EDCI (478 mg, 2.497 mmol) was added. The reaction was stirred for 30 minutes at −15° C. and then allowed to warm to room temperature, (R)-methyl 2-amino-3-methylbutanoate hydrochloride (417 mg, 2.497 mmol) was added. After being stirred overnight, the reaction mixture was concentrated under vacuum; the residue was diluted with EtOAc and washed with brine. The combined organic layers were dried and concentrated; the residue was purified by silica gel column chromatography to give the title compound as colourless oil (900 mg, 84%).
Workup
- temperatureto warm to room temperature
- stirringAfter being stirred overnight
- concentrationthe reaction mixture was concentrated under vacuum
- additionthe residue was diluted with EtOAc
- washwashed with brine
- customThe combined organic layers were dried
- concentrationconcentrated
- customthe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-4c49c68b29ab4d18a1968e08a0a7976b
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08022092B2
Linked notes
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