Tetrahydrofuran → 3-[4-(4-Acetyl-2-fluoro-phenyl)-piperazine-1-carbonyl]-4-azepan-1-yl-benzonitrile

HRID 32662

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=3Br)[C:21]#[N:22])=[O:17])[CH2:12][CH2:11]2)=[C:6]([F:27])[CH:5]=1)(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.[NH:37]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.C1COCC1>CN(C=O)C>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=3[N:37]3[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]3)[C:21]#[N:22])=[O:17])[CH2:12][CH2:11]2)=[C:6]([F:27])[CH:5]=1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 30.1 mg (0.7 mmol) 3-[4-(4-Acetyl-2-fluoro-phenyl)-piperazine-1-carbonyl]-4-bromo-benzonitrile, 30 ul (0.175 mmol) DIPEA and 91 ul (0.91 mmol) of a 1M solution of azepane in DMF was heated to 100° C. for 24 h. After removal of THF 2 ml dioxane, 180 ul of a 1M solution of azepane in DMF and 30 ul (0.175 mmol) DIPEA were added and the mixture was heated to 120° C. for 16 h. After evaporation of all volatiles the residue was taken up in 1 ml MeOH/formic acid 6/1 and subjected to reversed phase HPLC purification eluting with an acetonitrile/water gradient to yield after evaporation of the product fractions 9.3 mg (30%) of the title compound. MS (m/e): 449.2 (MH+, 100%)

Workup

additionwere added
temperaturethe mixture was heated to 120° C. for 16 h
customAfter evaporation of all volatiles the residue
customsubjected to reversed phase HPLC purification
washeluting with an acetonitrile/water gradient
customto yield
customafter evaporation of the product fractions 9.3 mg (30%) of the title compound

Sources & evidence

ORD record: ord-a57e187189634134a1f8a34fd3c57b41
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07427612B2

Linked notes

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