Diisopropylethylamine → HCID 178424314, compound

HRID 243347Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (S)-1-(3-o-tolyl-3H-imidazo[4,5-b]pyridin-2-yl)ethylamine (330 mg, 1.31 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (430 mg, 1.83 mmol) and DIPEA (0.41 mL, 2.35 mmol) in n-butanol (2 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) to afford 168 as a white solid (155 mg, 32%). LCMS (Method K): RT 2.70 and 2.83 min [M+H]+ 371.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.89 (1H, s), 8.30-7.86 (4H, m), 7.69-7.08 (5H, m), 5.47 (1H, s), 1.96 (3H, s), 1.68 (1.5H, d, J=6.77 Hz), 1.50 (1.5H, d, J=6.84 Hz). Signals split due to presence of rotamers/tautomers.

Workup

temperatureAfter cooling to RT
customthe crude reaction mixture
washwashed with MeOH
additionThe product containing fractions
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-9d5c47e0ddb14f8aa954a9054738d5a3
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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