Phenethyl bromide → HCID 44434067, compound

HRID 130879Notes

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][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C=O)C>[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)[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

Conditions

Temperature: 75 °C

Procedure

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Part E, 112.9 mg, 0.40 mmol), K2CO3 (110.1 mg, 0.80 mmol), and phenethyl bromide (82 uL 0.60 mmol) in DMF (2.0 mL). Heat at 70-80° C. overnight. Remove DMF azeotropically with xylenes. Purify by flash chromatography, eluting with 75:19:6 EtOAc/CH2Cl2/2.0 M NH3 in MeOH and then with 60:30:10 EtOAc/hexanes/2.0 M NH3 in MeOH. Purify by reverse phase chromatography, eluting with 0-99% 0.1% TFA/acetonitrile and 0.1% TFA/water to give the title compound (44.9 mg, 27% from Step D): MS ES+ 284.0 (M−H)+; 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, 5-95% over 19 min], tR=9.85 min, 100% purity; Anal. Calcd for C24H25N3O2.0.1H2O.0.1MeOH: C, 73.75; H, 6.57; N, 10.71. Found: C, 73.45; H, 6.62; N, 10.72.

Workup

customPurify by flash chromatography
washeluting with 75:19:6 EtOAc/CH2Cl2/2.0 M NH3 in MeOH
customPurify by reverse phase chromatography
washeluting with 0-99% 0.1% TFA/acetonitrile and 0.1% TFA/water

Sources & evidence

ORD record: ord-ca71ab54daf5466c952947ee060e18c6
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07381719B2

Reaction notes

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