Cesium carbonate → 9-(Cyclopropylmethyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 875979Notes

Reaction equation

C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:50]1[C:51]([F:68])=[N:52][CH:53]=[CH:54][C:55]=1[C:56]1[C:57]([NH:63][CH2:64][CH:65]2[CH2:67][CH2:66]2)=[N:58][C:59]([NH2:62])=[N:60][CH:61]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:65]1([CH2:64][N:63]2[C:57]3[N:58]=[C:59]([NH2:62])[N:60]=[CH:61][C:56]=3[C:55]3[CH:54]=[CH:53][N:52]=[C:51]([F:68])[C:50]2=3)[CH2:67][CH2:66]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a vacuum to argon purged vial containing 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.017 g, 0.030 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.014 g, 0.015 mmol), cesium carbonate (0.19 g, 0.59 mmol) and compound 240 (0.100 g, 0.30 mmol) was added degassed dioxane (2.00 mL). The reaction was stirred at 100° C. After 4 h, the reaction was cooled and applied directly to silica. Silica gel chromatography (gradient elution 40 to 90% ethyl acetate in hexanes) afforded compound 241 (0.060 g, 79% yield). 1H NMR (500 MHz, CDCl3) δ ppm 0.45-0.57 (m, 4 H) 1.34-1.47 (m, 1 H) 4.32 (d, J=7.09 Hz, 2 H) 5.46 (br. s., 2 H) 7.68 (dd, J=5.26, 2.81 Hz, 1 H) 8.02 (dd, J=5.13, 1.71 Hz, 1 H) 8.93 (s, 1 H).

Workup

additionwas added
customdegassed dioxane (2.00 mL)
temperaturethe reaction was cooled
washSilica gel chromatography (gradient elution 40 to 90% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-29f3bc1f545f435782629b536169336e
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08980903B2

Reaction notes

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