Diisopropylethylamine → HCID 178461927, compound

HRID 243455Notes

Reaction equation

[CH:1]1([N:4]2[C:8]3[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=3[N:6]=[C:5]2[C@@H:14]([NH2:16])[CH3:15])[CH2:3][CH2:2]1.Cl[C:18]1[N:26]=[CH:25][N:24]=[C:23]2[C:19]=1[N:20]=[CH:21][N:22]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[CH:1]1([N:4]2[C:8]3[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=3[N:6]=[C:5]2[C@@H:14]([NH:16][C:18]2[N:26]=[CH:25][N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)[CH3:15])[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (S)-1-(1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamine (166 mg, 0.76 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (180 mg, 0.76 mmol) and DIPEA (0.7 mL, 3.8 mmol) in n-butanol (3 mL) was heated at 100° C. for 18 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 0-10% 2M NH3/MeOH in DCM) to afford 374 as a white solid (125 mg, 49%). LCMS (Method K): RT 2.72 min [M+H]+ 338.1. 1H NMR (DMSO-d6, 400 MHz): δ 8.23-8.09 (2H, m), 7.90 (1H, br s), 7.56 (1H, dd, J=8.77, 4.94 Hz), 7.37 (1H, dd, J=9.27, 2.53 Hz), 7.05-6.97 (1H, m), 5.94 (1H, br s), 3.43-3.36 (1H, m), 1.69 (3H, d, J=6.80 Hz), 1.33-1.00 (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-bf3429505c3d42b597d94574f0d09dbd
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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