Diisopropylethylamine → {(3R,4S)-4-(4-Chloro-phenyl)-1-[1-(5-cyano-pyrimidin-2-yl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester

HRID 527481

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:13]2[C@@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[CH2:16][N:15]([C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:26])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1.Cl[C:35]1[N:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][N:36]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:13]2[C@@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[CH2:16][N:15]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:35]4[N:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][N:36]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 94.7 mg (0.2 mmol)[(3R,4S)-4-(4-Chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester, 83.7 mg (0.3 mmol) 2-chloropyrimidine-5-carbonitrile and 129 mg (1 mmol) DIPEA in 2.5 mL DMF was shaken a for 22 h at 65° C. The mixture was subjected to preparative HPLC purification on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fraction were evaporated to access 58 mg (51%) of the title compound as off-white solid. MS m/e: 577.3 [M+H]+.

Workup

customThe mixture was subjected to preparative HPLC purification on reversed phase
washeluting with a gradient
customformed from acetonitrile, water and NEt3
additionThe product containing fraction
customwere evaporated

Sources & evidence

ORD record: ord-7d1abb71843748acb87097cbf899d5a9
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346786B2

Linked notes

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