4-Methoxybenzylamine → [7-Bicyclo[1.1.1]pent-1-yl-2-(4-methoxy-benzylamino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-(5-bromo-pyridin-3-yl)-methanone

HRID 82300Notes

Reaction equation

[C:1]12([N:6]3[C:10]4[N:11]=[C:12](Cl)[N:13]=[CH:14][C:9]=4[C:8]([C:16]([C:18]4[CH:19]=[N:20][CH:21]=[C:22]([Br:24])[CH:23]=4)=[O:17])=[CH:7]3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.[CH3:25][O:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31][NH2:32])=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:1]12([N:6]3[C:10]4[N:11]=[C:12]([NH:32][CH2:31][C:30]5[CH:33]=[CH:34][C:27]([O:26][CH3:25])=[CH:28][CH:29]=5)[N:13]=[CH:14][C:9]=4[C:8]([C:16]([C:18]4[CH:19]=[N:20][CH:21]=[C:22]([Br:24])[CH:23]=4)=[O:17])=[CH:7]3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of (7-Bicyclo[1.1.1]pent-1-yl-2-chloro-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(5-bromo-pyridin-3-yl)-methanone (Preparation 284, 1.1 g, 2.72 mmol) and 4-methoxy benzyl amine (1.06 mL, 8.16 mmol) in dioxane (40 mL), DIPEA (1.7 mL, 10.8 mmol) was added and mixture was heated at 110° C. under microwave irradiation for 6 hours. The volatiles were removed in vacuo and the residue was partitioned between water (50 mL) ethyl acetate (150 mL). Organic phase was dried over sodium sulphate, evaporated in vacuo and purified by column chromatography on silica gel (gradient of EA:Hexane 25:75) to afford the title compound as off white solid in 84% yield, 1.15 g.

Workup

customThe volatiles were removed in vacuo
customthe residue was partitioned between water (50 mL) ethyl acetate (150 mL)
dry with materialOrganic phase was dried over sodium sulphate
customevaporated in vacuo
custompurified by column chromatography on silica gel (gradient of EA:Hexane 25:75)

Sources & evidence

ORD record: ord-f63f92841f464ab39f30dac9378a8b81
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846698B2

Reaction notes

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