Cesium carbonate → (S)-tert-butyl (4-methyl-1-((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate

HRID 870978Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[C:13]([CH3:16])[CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1.[OH:17][CH2:18][C@@H:19]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH:21]([CH3:23])[CH3:22].C([O-])([O-])=O.[Cs+].[Cs+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:22][CH:21]([CH3:23])[CH2:20][C@H:19]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:18][O:17][C:2]1[CH:3]=[CH:4][C:5]2[C:15]3[C:10](=[CH:11][N:12]=[C:13]([CH3:16])[CH:14]=3)[CH2:9][O:8][C:6]=2[CH:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 8-chloro-2-methyl-5H-chromeno[3,4-c]pyridine (0.2 g, 0.863 mmol), (S)-tert-butyl (1-hydroxy-4-methylpentan-2-yl)carbamate (0.225 g, 1.036 mmol), palladium(II) acetate (5.81 mg, 0.026 mmol), Cs2CO3 (0.422 g, 1.295 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.022 g, 0.052 mmol) in toluene (5 mL) was heated to 110° C. for 18 h. After cooling, the mixture was filtered through celite and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (70% EtOAc in pet. ether) to afford (S)-tert-butyl (4-methyl-1-((2-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate, as a semi-solid (0.12 g, 0.291 mmol, 34% yield). LCMS (ESI) m/e 413.4 [(M+H)+, calcd for C24H33N2O4 413.2]; LC/MS retention time (Method D): tR=2.42 min.

Workup

temperatureAfter cooling
filtrationthe mixture was filtered through celite and
concentrationconcentrated under reduced pressure
customThe crude product was purified by silica gel chromatography (70% EtOAc in pet. ether)

Sources & evidence

ORD record: ord-2382b32b1eca42759136ea5000db3553
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969564B2

Reaction notes

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