Methoxymethyl-triphenylphosphonium chloride → 5-[5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ylamine

To a suspension of (methoxymethyl)triphenylphosphonium chloride (166 mg, 0.485 mmol) in THF (1 ml) at 0° C. under nitrogen was added potassium bis(trimethylsilyl)amide (97 mg, 0.485 mmol). The mixture was stirred at room temperature for 30 min, then it was added to [2-amino-5-(3,4-dimethoxy-phenyl)-pyridin-3-yl]-(6-amino-pyridin-3-yl)-methanone (34 mg, 0.097 mmol) in one portion. The reaction mixture was stirred for 2 hours, then quenched with wet methanol and concentrated in vacuo. The crude was diluted with 2 ml of 1,4-dioxane and treated with 0.1 ml of aqueous 70% perchloric acid. The mixture was stirred at 80° C. for 19 hours, diluted with THF/methanol (1:1), and treated with 2.0 g of PS-trisamine (Argonaut Technologies, 4 equivalents per equivalent of acid used) for 30 minutes. The resin was filtered off and washed with THF-MeOH (1:1). Purification was accomplished by flash chromatography on silica gel with a gradient, of methanol/dichloromethane afforded 5-[5-(3,4-dimethoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-pyridin-2-ylamine as a yellow solid (9.7 mg, 29% yield). 1H NMR (DMSO-d6): δ 11.8 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 8.31 (d, J=2.0 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 7.77 (dd, J=2.0, 10.0 Hz, 1H), 7.70 (d, J=2.5 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 7.24 (dd, J=2.0, 7.5 Hz, 1H), 7.04 (d, J=8.5 Hz, 1H), 6.55 (d, J=8.5 Hz, 1H), 5.90 (broad s, 2H), 3.86 (s, 3H), 3.79 (s, 3H). HPLC/MS m/z 347.1 [MH]+.

1. stirringThe reaction mixture was stirred for 2 hours
2. customquenched with wet methanol
3. concentrationconcentrated in vacuo
4. additionThe crude was diluted with 2 ml of 1,4-dioxane
5. additiontreated with 0.1 ml of aqueous 70% perchloric acid
6. stirringThe mixture was stirred at 80° C. for 19 hours
7. additiondiluted with THF/methanol (1:1)
8. additiontreated with 2.0 g of PS-trisamine (Argonaut Technologies, 4 equivalents per equivalent of acid used) for 30 minutes
9. filtrationThe resin was filtered off
10. washwashed with THF-MeOH (1:1)
11. customPurification

ORD record

ord-1b4065c63c874bf093ec218afeac2f8b

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07906648B2