Diisopropylethylamine → HCID 178493008, compound

HRID 243470Notes

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-(cis-3-methoxycyclobutyl)-1H-benzoimidazol-2-yl]ethylamine (160 mg, 0.61 mmol) in IPA (1.5 mL) was added 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (150 mg, 0.61 mmol) and DIPEA (0.53 mL, 3.1 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 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 396 as a white solid (120 mg, 52%). 1H NMR 6 (DMSO-d6): 8.24 (1H, s), 8.14 (1H, s), 7.90 (1H, d, J=7.84 Hz), 7.63 (1H, dd, J=8.82, 5.11 Hz), 7.54 (1H, dd, J=9.80, 2.47 Hz), 7.11-7.02 (1H, m), 5.84 (1H, s), 4.99-4.89 (1H, m), 3.81-3.72 (1H, m), 3.23 (3H, s), 2.96-2.59 (4H, m), 1.64 (3H, d, J=6.70 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-ec26d2ed47084c338e58484233b2d609
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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