Diisopropylethylamine → HCID 178461928, compound

HRID 243454Notes

Reaction equation

[CH:1]1([N:5]2[C:9]3[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=3[N:7]=[C:6]2[C@@H:15]([NH2:17])[CH3:16])[CH2:4][CH2:3][CH2:2]1.Cl[C:19]1[N:27]=[CH:26][N:25]=[C:24]2[C:20]=1[N:21]=[CH:22][N:23]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[CH:1]1([N:5]2[C:9]3[CH:10]=[C:11]([F:14])[CH:12]=[CH:13][C:8]=3[N:7]=[C:6]2[C@@H:15]([NH:17][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:16])[CH2:2][CH2:3][CH2:4]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (S)-1-(1-cyclobutyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamine (251 mg, 1.1 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (260 mg, 1.1 mmol) and DIPEA (1.0 mL, 5.5 mmol) in n-butanol (4 mL) was heated at 100° C. for 18 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 0-10% 2M NH3/MeOH in DCM) to afford 373 as a white solid (140 mg, 36%). LCMS (Method K): RT 2.93 min [M+H]+ 352.1 1H NMR (DMSO-d6, 400 MHz): δ 12.97 (1H, br), 8.33-7.76 (3H, m), 7.69-7.53 (2H, m), 7.09-6.98 (1H, m), 5.87 (1H, br s), 5.27-5.14 (1H, m), 2.93-2.72 (2H, m), 2.44 (1H, br s), 2.23 (1H, br s), 2.02-1.89 (1H, m), 1.82-1.61 (4H, m)

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 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record: ord-6c496bf7ac7c4849b9dd09f0bdf1968a
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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