4-Chloropyridine hydrochloride → 3-Methyl-5-phenylmethoxy-1-(4-pyridinylamino)-1H-indole

HRID 1029730Notes

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.Cl.Cl[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:9]=2)[N:4]([NH:19][C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)[CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution consisting of 3-methyl-5-(phenylmethoxy)-1H-indol-1-amine (6.31 g) and 1-methyl-2-pyrrolidinone (109 ml) was added 4-chloropyridine hydrochloride (3.94 g). The resulting mixture was heated at 80° C. for 4-5 hours. Another batch of reaction was also carried out with the amine (2.94 g) and 4-chloropyridine hydrochloride (1.84 g) in nmp (50 ml) at 80° C. for 4 hours. The above reaction mixtures were poured together into dilute aqueous sodium bicarbonate and extracted with EtOAc (4×) and ether (1×). The combined organic layers were washed with water and brine followed by drying (K2CO3). Filtration, concentration and purification via flash column chromatography (silica gel, 2% Et3N/ether/0-5% MeOH) afforded 7.55 g of the desired product. Recrystallization from EtOAc gave a solid, m.p. 167.5°-169.5° C.

Workup

customAnother batch of reaction
customThe above reaction mixtures
extractionextracted with EtOAc (4×) and ether (1×)
washThe combined organic layers were washed with water and brine
dry with materialby drying (K2CO3)
filtrationFiltration, concentration and purification via flash column chromatography (silica gel, 2% Et3N/ether/0-5% MeOH)

Sources & evidence

ORD record: ord-7a4ed6a2e43c41c0be33f564f33ab2bd
Source dataset: uspto-grants-1992_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05102891

Reaction notes

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