Diisopropylethylamine → HCID 178461900, compound

HRID 243349Notes

Reaction equation

[NH2:1][C@H:2]([C:4]1[N:8]([C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])[C:7]2[CH:17]=[CH:18][CH:19]=[CH:20][C:6]=2[N:5]=1)[CH3:3].Cl[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[N:30]1[C:22]([NH:1][C@H:2]([C:4]2[N:8]([C:9]3[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=3)[C:12]#[N:13])[C:7]3[CH:17]=[CH:18][CH:19]=[CH:20][C:6]=3[N:5]=2)[CH3:3])=[C:23]2[C:27]([NH:26][CH:25]=[N:24]2)=[N:28][CH:29]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 3-[2-((S)-1-aminoethyl)benzoimidazol-1-yl]benzonitrile (54 mg, 0.21 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (69 mg, 0.29 mmol) and DIPEA (65 mL, 0.37 mmol) in n-butanol (0.5 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) then by preparative HPLC (Phenomenex Gemini 5 μm C18 on a gradient 20-98%, 0.1% HCO2H in acetonitrile/water) to afford 170 as a white solid (29 mg, 37%). LCMS (Method K): RT 3.03 min [M+H]+ 381.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.90 (1H, s), 8.25-7.49 (8H, m), 7.32-7.17 (2H, m), 7.09 (1H, d, J=7.84 Hz), 5.60 (1H, s), 1.64 (3H, d, J=6.81 Hz)

Workup

temperatureAfter cooling to RT
customthe crude reaction mixture
washwashed with MeOH
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record: ord-8c227ac7142a49f5b3242c37b516a424
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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