Potassium Carbonate → HCID 71093636, compound

HRID 72707Notes

Reaction equation

[F:1][CH:2]1[CH2:5][N:4]([C:6]2[N:11]=[CH:10][N:9]=[C:8]3[N:12]([CH3:21])[N:13]=[C:14]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[C:7]=23)[CH2:3]1.Br[C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:31][CH2:30]2)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:29]1([C:26]2[CH:27]=[CH:28][C:23]([C:19]3[N:18]([CH3:20])[N:17]=[CH:16][C:15]=3[C:14]3[C:7]4[C:8](=[N:9][CH:10]=[N:11][C:6]=4[N:4]4[CH2:3][CH:2]([F:1])[CH2:5]4)[N:12]([CH3:21])[N:13]=3)=[CH:24][CH:25]=2)[CH2:31][CH2:30]1

Participants

Conditions

Temperature: 100 °C

Procedure

4-(3-Fluoroazetidin-1-yl)-1-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidine (C11) (300 mg, 1.04 mmol), 1-bromo-4-cyclopropylbenzene (617 mg, 3.13 mmol), and potassium carbonate (289 mg, 2.09 mmol) were combined in 1,4-dioxane (7 mL). Palladium(II) acetate (98%, 50.2 mg, 0.219 mmol) was added, and the reaction mixture was heated at 100° C. for 48 hours. Solids were removed via filtration, and the filtrate was concentrated in vacuo. Purification using silica gel chromatography [Gradient: 25% to 50% (10% methanol in ethyl acetate) in heptane] provided the product as a glass. Yield: 205.3 mg, 0.509 mmol, 49%. LCMS m/z 404.2 (M+1). 1H NMR (400 MHz, CD3OD) δ 0.61-0.66 (m, 2H), 0.91-0.97 (m, 2H), 1.81-1.89 (m, 1H), 3.77-3.95 (br m, 2H), 3.91 (s, 3H), 3.95 (s, 3H), 4.07-4.26 (br m, 2H), 5.15-5.36 (m, 1H, JHF=57.5 Hz), 7.05 (br d, J=8.2 Hz, 2H), 7.23 (br d, J=8.4 Hz, 2H), 7.71 (s, 1H), 8.20 (s, 1H).

Workup

customSolids were removed via filtration
concentrationthe filtrate was concentrated in vacuo
customPurification

Sources & evidence

ORD record: ord-2c8bf715a7294907a3759e0d6c197395
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829010B2

Reaction notes

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