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

HRID 528040Notes

Reaction equation

[CH3:1][N:2]1[C:10]([C:11]2[CH:12]=[N:13][NH:14][CH:15]=2)=[N:9][C:8]2[C:3]1=[N:4][CH:5]=[N:6][C:7]=2[N:16]1[CH2:21][CH2:20][CH:19]([N:22]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[NH:24][C:23]2=[O:31])[CH2:18][CH2:17]1.Br[CH2:33][CH:34]1[CH2:37][CH2:36][CH2:35]1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH:34]1([CH2:33][N:13]2[CH:12]=[C:11]([C:10]3[N:2]([CH3:1])[C:3]4[C:8]([N:9]=3)=[C:7]([N:16]3[CH2:17][CH2:18][CH:19]([N:22]5[C:26]6[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=6[NH:24][C:23]5=[O:31])[CH2:20][CH2:21]3)[N:6]=[CH:5][N:4]=4)[CH:15]=[N:14]2)[CH2:37][CH2:36][CH2:35]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 1-{1-[9-methyl-8-(1H-pyrazol-4-yl)-9H-purin-6-yl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one (30 mg, 0.07 mmol) in DMF (0.5 mL) were added (bromomethyl)cyclobutane (0.02 mL, 0.18 mmol), and sodium bicarbonate (9 mg, 0.11 mmol). The reaction mixture was heated to 100° C. for 24 hours. The product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to give 7 mg (23% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 10.85 (s, 1H), 8.42 (s, 1H), 8.25 (s, 1H), 8.01 (t, 1H), 7.13 (dd, 1H), 6.95-6.90 (m, 3H), 4.62-4.45 (m, 1H), 4.21 (d, 2H), 3.86-3.82 (m, 3H), 2.79 (dt, 1H), 2.40-2.25 (m, 2H), 2.01-1.92 (m, 2H), 1.87-1.70 (m, 6H); MS (EI) for C26H29N9O: 484.5 (MH+).

Workup

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

Sources & evidence

ORD record: ord-0e2c4b0cf3ab461595658dcc24e045af
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346807B2

Reaction notes

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