Diisopropylethylamine → HCID 178493008, compound

HRID 243471Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([C@H:13]3[CH2:16][C@H:15]([O:17][CH3:18])[CH2:14]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>CC(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H: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]([CH:13]3[CH2:16][CH:15]([O:17][CH3:18])[CH2:14]3)[C:6]=2[CH:19]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of (S)-1-[6-fluoro-1-(trans-3-methoxycyclobutyl)-1Hbenzoimidazol-2-yl]ethylamine (79 mg, 0.3 mmol) in IPA (1 mL) was added 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (72 mg, 0.3 mmol) and DIPEA (0.26 mL, 1.5 mmol) and the reaction mixture heated at 90° C. for 16 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue was 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 0-5% MeOH in DCM) to afford 397 as a white solid (37 mg, 32%). 1H NMR δ (DMSO-d6): 12.82 (1H, s), 8.25 (1H, s), 8.14 (1H, s), 7.92 (1H, s), 7.67-7.57 (2H, m), 7.05 (1H, td, J=9.30, 2.38 Hz), 5.86 (1H, s), 5.44-5.33 (1H, m), 4.17 (1H, t, J=6.72 Hz), 3.12 (3H, s), 3.07-2.96 (1H, m), 2.88-2.86 (1H, m), 2.56-2.45 (1H, m), 2.27-2.18 (1H, m), 1.65 (3H, d, J=6.69 Hz)

Workup

temperatureAfter cooling to RT
customthe volatiles were removed under reduced pressure
washThe cartridge was washed with MeOH
concentrationconcentrated in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record: ord-cb5c6bb5e4644737bcab0a4a1ad5c247
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

Loading…