O-Phenylenediamine → N1-(8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-6-morpholino-9H-purin-2-yl)benzene-1,2-diamine

HRID 1922941Notes

Reaction equation

Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([C:19]([O:22][CH3:23])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:3]=1.[C:30]1([NH2:37])[C:31]([NH2:36])=[CH:32][CH:33]=[CH:34][CH:35]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:23][O:22][C:19]([CH:16]1[CH2:17][CH2:18][N:13]([CH2:12][C:7]2[N:8]([CH3:11])[C:9]3[C:5]([N:6]=2)=[C:4]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[N:3]=[C:2]([NH:36][C:31]2[C:30]([NH2:37])=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:10]=3)[CH2:14][CH2:15]1)([CH3:21])[CH3:20]

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 4-(2-chloro-8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-9H-purin-6-yl)morpholine (1.21 g, 2.96 mmol), benzene-1,2-diamine (520 mg, 4.8 mmol), palladium acetate (66 mg, 0.29 mmol), bist(tri-t-butylphosphine)palladium (150 mg, 0.29 mmol) and sodium t-butoxide (620 mg, 6.4 mmol) in toluene (30 mL) was stirred at 95° C. for 18 hours. The reaction mixture was then filtered through paper and then concentrated. The crude product was then purified by flash chromatography using a Biotage KP-NH column (0-10% gradient MeOH in DCM) to give N1-(8-((4-(2-methoxypropan-2-yl)piperidin-1-yl)methyl)-9-methyl-6-morpholino-9H-purin-2-yl)benzene-1,2-diamine (1.2 g, 84%). LCMS: M+H+=481.2.

Workup

filtrationThe reaction mixture was then filtered through paper
concentrationconcentrated
customThe crude product was then purified by flash chromatography

Sources & evidence

ORD record: ord-58f59f5e302341899bb2a4fb9f457f7f
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173650B2

Reaction notes

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