Potassium Phosphate, Tribasic → 1-[1-(9-Methyl-8-pyridin-3-yl-9H-purin-6-yl)piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 528052Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Br[C:11]1[N:12]([CH3:36])[C:13]2[C:18]([N:19]=1)=[C:17]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]3[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[NH:28][C:27]3=[O:35])[CH2:22][CH2:21]1)[N:16]=[CH:15][N:14]=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:36][N:12]1[C:11]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[N:19][C:18]2[C:13]1=[N:14][CH:15]=[N:16][C:17]=2[N:20]1[CH2:21][CH2:22][CH:23]([N:26]2[C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[NH:28][C:27]2=[O:35])[CH2:24][CH2:25]1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of pyridin-3-ylboronic acid (50 mg, 0.41 mmol, Maybridge) in dioxane (0.75 mL) and water (0.1 mL) were added 1-(1-(8-bromo-9-methyl-9H-purin-6-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (50 mg, 0.12 mmol), Pd(dppf)Cl2 (20 mg, 0.02 mmol), and tribasic potassium phosphate (75 mg, 0.36 mmol). The reaction mixture was heated in a microwave reactor to 150° C. for 20 min. The product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to give 15 mg (29.3% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 10.84 (s, 1H), 9.03 (m, 1H), 8.72 (dd, 1H), 8.32 (m, 1H), 8.25 (m, 1H), 7.59 (ddd, 1H), 7.15 (m, 1H), 6-91 (m, 3H), 4.55 (t, 1H), 3.85 (s, 3H), 2.35 (m, 2H), 1.84 (d, 2H); MS (EI) for C23H22N8O: 427.4 (MH+).

Workup

customThe product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid)

Sources & evidence

ORD record: ord-89dd70272b7b4a3d90c2a689adaafc35
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346807B2

Reaction notes

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