N-methyl-2-pyrrolidone → 1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-5-(phenylmethoxy)-1H-indole

HRID 1029736Notes

Reaction equation

[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:9]=2)[N:4]([NH2:19])[CH:3]=1.CN1CCCC1=O.Cl.Cl[C:29]1[CH:34]=[CH:33][N:32]=[CH:31][C:30]=1[F:35].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:35][C:30]1[CH:31]=[N:32][CH:33]=[CH:34][C:29]=1[NH:19][N:4]1[C:5]2[C:10](=[CH:9][C:8]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:7][CH:6]=2)[C:2]([CH3:1])=[CH:3]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution consisting of 3-methyl-5-(phenylmethoxy)-1H-indol-1-amine (4.81 g) and 1-methyl-2-pyrrolidinone (83 ml) was added 4-chloro-3-fluoro pyridine hydrochloride (3.20 g). The resulting mixture was heated at 80° C. for 2 hours. Upon cooling to room temperature, dilute aqueous sodium bicarbonate and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous phase was extracted with EtOAc (3x). The combined organic layers were washed successively with water (2x) and brine (1x), and thereafter dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 50% ethyl acetate/dichloromethane) afforded 4.0 g of the desired product as a solid, m.p. 210°-213° C.

Workup

temperatureUpon cooling to room temperature
customThe layers were separated
extractionthe aqueous phase was extracted with EtOAc (3x)
washThe combined organic layers were washed successively with water (2x) and brine (1x)
dry with materialdried (MgSO4)
filtrationFiltration and concentration
customgave the crude product
customPurification via flash column chromatography (silica gel, 50% ethyl acetate/dichloromethane)

Sources & evidence

ORD record: ord-955271f5865940cca5a7f76918920b6f
Source dataset: uspto-grants-1992_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05102891

Reaction notes

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