Diisopropylethylamine → HCID 178448884, compound

HRID 243378Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:14])[CH:11]([CH3:13])[CH3:12])[N:7]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[C:6]=2[CH:21]=1.Cl[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]([NH:14][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][NH:27]4)[CH:11]([CH3:13])[CH3:12])[N:7]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[C:6]=2[CH:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)-2-methylpropylamine (135 mg, 0.48 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (110 mg, 0.48 mmol) and DIPEA (0.4 mL, 2.4 mmol) in n-butanol (2 mL) was heated for 18 h at 100° C. in a sealed vial. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue 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 was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) to afford 206 (75 mg, 39%). LCMS (Method K): RT 3.19 min [M+H]+ 403.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.85 (1H, s), 8.86-8.59 (2H, m), 8.18-7.88 (3H, m), 7.79-7.47 (3H, m), 7.11 (1H, td, J=9.31, 2.48 Hz), 6.93 (1H, br d, J=8.83 Hz), 5.21 (1H, br s), 0.99-0.90 (4H, m), 0.85 (3H, br s)

Workup

temperatureAfter cooling to RT
customthe volatiles were removed under reduced pressure
washThe cartridge was washed 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-fb589e9bdf2745738f78f2dc8e0d9cd1
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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