1-Bromopentane → 6-(2-pentyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

HRID 130916Notes

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+].Br[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].C(OCC)(=O)C>CN(C=O)C>[CH2:29]([N:2]1[CH2:3][CH2:4][CH2:5][C:6]2[CH:11]=[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:9]=[CH:8][C:7]=2[CH2:1]1)[CH2:30][CH2:31][CH2:32][CH3:33]

Participants

Conditions

Temperature: 100 °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 1-bromopentane (0.176 g, 1.16 mmol) in DMF (5.3 mL). Beat at 70° C. overnight and then increase the temperature to 100° C. for additional two hours. 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 7% to 15% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound : MS ES+354.2 (M+H)+, HRMS calcd for C21H28N3O2 354.2182 (M+H)+, found 354.2188, time 0.53 min; Anal. Calcd for C21H27N3O2: C, 71.36; H, 7.70 N, 11.89. Found: C, 71.14; H, 7.60; N, 11.79.

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 7% to 15% (2.0 M NH3 in methanol) in ethyl acetate

Sources & evidence

ORD record: ord-90a50c085c42488695baced300be737c
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07381719B2

Reaction notes

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