Bromocyclopentane → HCID 53482367, compound

HRID 2036623Notes

Reaction equation

[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[NH:17][C:16]3[C:18]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:19][CH:20]=[CH:21][C:15]=3[N:14]=2)[CH3:12])[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][C@H:11]([C:13]2[N:14]([CH:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[C:15]3[CH:21]=[CH:20][CH:19]=[C:18]([S:22]([CH3:25])(=[O:24])=[O:23])[C:16]=3[N:17]=2)[CH3:12])[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-amino-6-(((1S)-1-(7-(methylsulfonyl)-1H-benzimidazol-2-yl)-ethyl)amino)-5-pyrimidinecarbonitrile (110 mg, 0.31 mmol) and cesium carbonate (100 mg, 0.31 mmol) was stirred at rt for 30 min in DMF (2 mL). At this time bromocyclopentane (92 μL, 0.62 mmol) was added. The mixture was stirred at 110° C. in a sealed flask for 18 h. The mixture was cooled to rt and concentrated under reduced pressure. Purification of the residue by flash chromatography over silica gel, using 0 to 10% gradient of MeOH in DCM-EtOAc (1:1) with 0.2% NH4OH as eluent gave 4-amino-6-(((1S)-1-(1-cyclopentyl-4-(methylsulfonyl)-1H-benzimidazol-2-yl)ethyl)amino)-5-pyrimidinecarbonitrile: 1H NMR (400 MHz, DMSO-d6) δ 8.09 (1H, s), 7.95 (1H, s), 7.94 (1H, d, J=8.0 Hz), 7.72 (1H, d, J=8.0 Hz), 7.43 (1H, t, J=8.0 Hz), 7.35 (2H, br), 5.93-5.85 (1H, m), 5.03-4.95 (1H, m), 3.54 (3H, s), 2.70-2.66 (1H, m), 2.35-2.32 (1H, m), 2.18-1.94 (6H, m), 1.67 (3H, d, J=8.0 Hz); LC-MS (ESI) m/z 426.1 [M+H]+.

Workup

temperatureThe mixture was cooled to rt
concentrationconcentrated under reduced pressure
customPurification of the residue by flash chromatography over silica gel

Sources & evidence

ORD record: ord-28a3999f7e9d4fd3b6e7c9528e674040
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575183B2

Reaction notes

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