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

HRID 528039Notes

Reaction equation

[NH:1]1[CH:5]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:3]=[N:2]1.Br[C:16]1[N:17]([CH3:41])[C:18]2[C:23]([N:24]=1)=[C:22]([N:25]1[CH2:30][CH2:29][CH:28]([N:31]3[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=4[NH:33][C:32]3=[O:40])[CH2:27][CH2:26]1)[N:21]=[CH:20][N:19]=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]>[CH3:41][N:17]1[C:16]([C:4]2[CH:5]=[N:1][NH:2][CH:3]=2)=[N:24][C:23]2[C:18]1=[N:19][CH:20]=[N:21][C:22]=2[N:25]1[CH2:26][CH2:27][CH:28]([N:31]2[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[NH:33][C:32]2=[O:40])[CH2:29][CH2:30]1

Participants

Conditions

Temperature: 180 °C

Procedure

To a solution of Pyrazole-4-boronic acid pinacol ester (181 mg, 0.93 mmol) in dioxane (1.5 mL) and water (0.2 mL) were added 1-(1-(8-bromo-9-methyl-9H-purin-6-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (100 mg, 0.23 mmol), Pd(dppf)Cl2 (19 mg, 0.02 mmol), and tribasic potassium phosphate (297 mg, 1.4 mmol). The reaction mixture was heated in a microwave reactor to 180° C. for 60 min. The product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to give 60 mg (62.8% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 13.40 (s, 1H), 10.81 (d, 1H), 8.42 (s, 1H), 8.19-8.00 (m, 1H), 7.13 (dd, 1H), 6.99-6.88 (m, 3H), 4.60-4.47 (m, 1H), 3.84 (s, 3H), 3.18 (t, 2H), 2.40-2.25 (m, 2H), 1.80 (t, 2H); MS (EI) for C21H21N9O: 416.4 (MH+).

Workup

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

Sources & evidence

ORD record: ord-ea0d8a725e11455ca2654098ad30a2ac
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346807B2

Reaction notes

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