Ethyl Acetate → HCID 44434088, compound

HRID 228372Notes

Reaction equation

[CH2:1]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:11][C:6]=2[CH2:5][CH2:4][CH2:3][NH:2]1.C([O-])([O-])=O.[K+].[K+].Cl.Cl[CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C(OCC)(=O)C>CN(C=O)C>[N:32]1([CH2:31][CH2:30][N:2]2[CH2:3][CH2:4][CH2:5][C:6]3[CH:11]=[C:10]([O:12][C:13]4[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=4)[CH:9]=[CH:8][C:7]=3[CH2:1]2)[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Participants

Conditions

Temperature: 90 °C

Procedure

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Example 447, Part E, 0.300 g, 1.06 mmol), K2CO3 (0.366 g, 2.65 mmol), and 4-(2-chloroethyl)morpholine hydrochloride (0.217 g, 1.16 mmol) in DMF (5.3 mL). Heat at 90° C. overnight. Cool the reaction mixture to room temperature and add ethyl acetate (150 mL). Wash with 1.0 N NaOH (1×50 mL), brine (1×50 mL), dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 10% to 20% (2.0 M NH3 in methanol) in acetone to give the title compound: MS ES+ 397.2 (M+H)+, HRMS calcd for C22H29N4O3 397.2240 (M+H)+, found 397.2223, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18 min], tR=5.6 min, 99.0% purity.

Workup

temperatureCool the reaction mixture to room temperature
washWash with 1.0 N NaOH (1×50 mL), brine (1×50 mL)
dry with materialdry the organic layer over Na2SO4
filtrationfilter
concentrationconcentrate
customPurify by flash chromatography
washeluting with 10% to 20% (2.0 M NH3 in methanol) in acetone

Sources & evidence

ORD record: ord-8aeca39795e2415b9173cee9d7521c8d
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07560463B2

Reaction notes

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