Diisopropylethylamine → 4-Amino-6-((S)-1-{6-fluoro-1-[(S)-1-(2-hydroxy-ethyl)-piperidin-3-yl]-1H-benzoimidazol-2-yl}-ethylamino)-pyrimidine-5-carbonitrile

HRID 243407Notes

Reaction equation

[NH2:1][C@H:2]([C:4]1[N:8]([C@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][CH2:16][OH:17])[CH2:10]2)[C:7]2[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:6]=2[N:5]=1)[CH3:3].[NH2:23][C:24]1[C:29]([C:30]#[N:31])=[C:28](Cl)[N:27]=[CH:26][N:25]=1.CCN(C(C)C)C(C)C>CC(O)C>[NH2:23][C:24]1[C:29]([C:30]#[N:31])=[C:28]([NH:1][C@H:2]([C:4]2[N:8]([C@H:9]3[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][CH2:16][OH:17])[CH2:10]3)[C:7]3[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:6]=3[N:5]=2)[CH3:3])[N:27]=[CH:26][N:25]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 2-{(S)-3-[2-((S)-1-aminoethyl)-6-fluorobenzoimidazol-1-yl]piperidin-1-yl}ethanol (35.6 mg, 0.12 mmol), 4-amino-6-chloropyrimidine-5-carbonitrile (18 mg, 0.12 mmol), and DIPEA (40 μL, 0.23 mmol) in IPA (1 mL) was stirred at 90° C. for 3 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (Si—PCC, gradient 2-10% 2M NH3/MeOH in DCM) affording 285 as a colourless solid (17 mg, 35%). LCMS (Method K): RT 2.24 min [M+H]+ 425.1. 1H NMR (CD3OD, 400 MHz): δ 8.06 (1H, s), 7.58 (1H, dd, J=8.9, 5.0 Hz), 7.49 (1H, dd, J=9.6, 2.4 Hz), 7.01 (1H, dt, J=9.2, 2.4 Hz), 5.84 (1H, q, J=6.9 Hz), 4.70-4.61 (1H, m), 3.63 (2H, t, J=6.0 Hz), 3.17-3.12 (1H, m), 3.01-2.96 (1H, m), 2.83 (1H, t, J=11.0 Hz), 2.66-2.54 (2H, m), 2.39-2.24 (2H, m), 1.99-1.88 (2H, m), 1.86-1.77 (1H, m), 1.70 (3H, d, J=6.9 Hz)

Workup

temperatureAfter cooling to RT
customvolatiles were removed under reduced pressure
customthe resulting residue purified by column chromatography (Si—PCC, gradient 2-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record: ord-27eaaf69cbc745e3bfaca427db27d44e
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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