Diisopropylethylamine → HCID 178463563, compound

HRID 243416Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]([NH2:12])[CH3:11])[N:7]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.Cl[C:21]1[N:29]=[CH:28][N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][N:25]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]([NH:12][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:11])[N:7]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-(6-fluoro-1-pyridin-4-yl-1H-benzoimidazol-2-yl)ethylamine (60 mg, 0.23 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (59 mg, 0.25 mmol) and DIPEA (125 μL, 0.70 mmol) in n-butanol (0.5 mL) was heated at 100° C. in a sealed vial for 23 h. After cooling to RT, the resulting mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a gradient 5-60%, 0.1% NH4OH in acetonitrile/water) to afford 303 as a pale orange solid (12 mg, 14%). LCMS (Method K): RT 2.70 min [M+H]+ 375.05. 1H NMR (DMSO-d6, 400 MHz): δ 12.90 (1H, s), 8.72-8.66 (2H, m), 8.09-8.01 (2H, m), 7.73-7.67 (3H, m), 7.19-7.01 (2H, m), 5.68-5.11 (1H, m), 1.62 (3H, d, J=7.26 Hz)

Workup

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

Sources & evidence

ORD record: ord-7f7a11f4b45248ce860a25022268c563
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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