Isopropanol → N-(3-Fluoro-4-pyridinyl)-3-methyl-1H-indol-1-amine

HRID 1197622Notes

Reaction equation

C(O)(C)C.Cl.Cl[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][C:8]=1[F:13].[CH3:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]([NH2:24])[CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>O>[F:13][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:7]=1[NH:24][N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([CH3:14])=[CH:16]1

Participants

Conditions

Temperature: 90 °C

Procedure

To 200 ml isopropanol was added 4-chloro-3-fluoropyridine hydrochloride (10 g) and 3-methyl-1H-indole-1-amine (5.9 g). The mixture was stirred at 90° C. for four hours, cooled; then poured into 500 ml iced-water, pH adjusted to 10 with Na2CO3 solution, then extracted with ethyl acetate. The organic layer was washed with water, then dried (saturated NaCl, anhydrous MgSO4). After filtering, the solvent was evaporated to an oil, which was eluted on a silica gel column with CH2Cl2 (DCM) then with ether:petroleum ether (1:1) via flash chromatography. The desired fractions were combined then evaporated to yield 6.2 g of a solid, m.p. 45° C. A sample of this material was recrystallized from isopropyl ether/hexanes (1:1) to give a solid, m.p. 141°-142° C.

Workup

temperaturecooled
extractionextracted with ethyl acetate
washThe organic layer was washed with water
dry with materialdried (saturated NaCl, anhydrous MgSO4)
filtrationAfter filtering
customthe solvent was evaporated to an oil, which
washwas eluted on a silica gel column with CH2Cl2 (DCM)
customThe desired fractions were combined then evaporated

Sources & evidence

ORD record: ord-f55f4f0d923e43fcbc7d8f8e1814c83e
Source dataset: uspto-grants-1994_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05276156

Reaction notes

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