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

HRID 130880Notes

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+].[CH2:28](Br)[CH2:29][CH:30]([CH3:32])[CH3:31]>CN(C=O)C>[CH3:31][CH:30]([CH3:32])[CH2:29][CH2:28][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

Participants

Conditions

Temperature: 80 °C

Procedure

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Example 447, Part E, 50.7 mg, 0.18 mmol), K2CO3 (49.5 mg, 0.36 mmol), and isoamyl bromide (32 uL, 0.27 mmol) in DMF (1.0 mL). Heat at 80° C. for 6 hours. Pass through an SCX column, washing with methanol and then eluting with 2.0 M NH3 in MeOH. Concentrate the eluant and purify by flash chromatography, eluting with 70:22:8 EtOAc/CH2Cl2/2.0 M NH3 in MeOH to afford the title compound (45.7 mg, 72%): MS ES+ 354.0 (M+H)+, HRMS calcd for C21H28N3O2 354.2182 (M+H)+, found 354.2182, time 0.39 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 20-99% over 23 min], tR=6.39 min, 100% purity; Anal. Calcd for C21H27N3O2.0.2CH2Cl2.0.1MeOH: C, 69.59; H, 5.98; N, 11.43. Found: C, 69.47; H, 6.25; N, 11.30.

Workup

washPass through an SCX column, washing with methanol
washeluting with 2.0 M NH3 in MeOH
concentrationConcentrate the eluant
custompurify by flash chromatography
washeluting with 70:22:8 EtOAc/CH2Cl2/2.0 M NH3 in MeOH

Sources & evidence

ORD record: ord-426502e386d245da8aff416ccc6da4fb
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07381719B2

Reaction notes

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