Ethyl 3-bromopropionate → Ethyl 3-[9-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl]propanoate

HRID 1514248Notes

Reaction equation

Cl.[CH3:2][CH:3]([O:5][C:6]1[CH:13]=[CH:12][C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[C:29]4[O:28][CH2:27][CH2:26][NH:25][CH2:24][C:23]=4[CH:22]=[CH:21][CH:20]=3)[N:15]=2)=[CH:10][C:7]=1[C:8]#[N:9])[CH3:4].C(N(CC)C(C)C)(C)C.Br[CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43]>C(#N)C>[C:8]([C:7]1[CH:10]=[C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[C:29]4[O:28][CH2:27][CH2:26][N:25]([CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:24][C:23]=4[CH:22]=[CH:21][CH:20]=3)[N:15]=2)[CH:12]=[CH:13][C:6]=1[O:5][CH:3]([CH3:2])[CH3:4])#[N:9]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1,4-benzoxazepin-9-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride (Example 32) (90 mg, 0.218 mmol) in acetonitrile (10 ml) was added N,N-diisopropylethylamine (0.076 ml, 0.436 mmol) followed by ethyl 3-bromopropanoate (0.056 ml, 0.436 mmol). The reaction mixture was heated at 80° C. overnight. A further 1 equivalent of N,N-diisopropylethylamine and ethyl 3-bromopropanoate were added and heating continued overnight. The reaction mixture was cooled and evaporated. Purification of the residue by column chromatography on silica, eluting with 60-70% ethyl acetate in cyclohexane to give the title compound as a brown oil (40 mg).

Workup

temperatureheating continued overnight
temperatureThe reaction mixture was cooled
customevaporated
customPurification of the residue by column chromatography on silica
washeluting with 60-70% ethyl acetate in cyclohexane

Sources & evidence

ORD record: ord-fbcbcb55f29b4cdf88f62918045e96bc
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222245B2

Reaction notes

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