4-Chlorophenylboronic acid → HCID 71513418, compound

HRID 920209Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:13]=[C:14]([N:18]([CH3:23])[C:19](=[O:22])[CH:20]=[CH2:21])[CH:15]=[CH:16][CH:17]=3)[N:9]=[C:10](I)[C:3]=12.[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:13]=[C:14]([N:18]([CH3:23])[C:19](=[O:22])[CH:20]=[CH2:21])[CH:15]=[CH:16][CH:17]=3)[N:9]=[C:10]([C:28]3[CH:29]=[CH:30][C:25]([Cl:24])=[CH:26][CH:27]=3)[C:3]=12

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of N-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl) phenyl)-N-methylacrylamide (50) (147 mg, 0.35 mmol) and 4-chlorophenylboronic acid (66 mg, 0.42 mmol) in DME/H2O (4 mL/1 mL) were added Pd(dppf)Cl2(14 mg, 0.018 mmol) and K3PO4.3H2O (280 mg, 1.05 mmol). The resulting mixture was purged with N2 (3×) and stirred at 80° C. overnight. Solvents were removed in vacuo. The residue was pre-purified by flash chromatography (silica gel, 0 to 10% MeOH in DCM with 0.3% TEA) and followed by prep HPLC to provide N-(3-(4-amino-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-N-methylacrylamide (51) (39 mg, 28%) as a white solid. LC-MS (ESI): m/z (M+1) 405.1. 1H NMR (400 MHz, DMSO) δ 8.40 (s, 1H), 8.26 (d, J=8.4 Hz, 1H), 8.14 (s, 1H), 7.76 (d, J=8.3 Hz, 2H), 7.62 (m, 3H), 7.28 (m, 1H), 6.17 (m, 2H), 5.59 (m, 1H), 3.30 (s, 3H).

Workup

customThe resulting mixture was purged with N2 (3×)
customSolvents were removed in vacuo
customThe residue was pre-purified by flash chromatography (silica gel, 0 to 10% MeOH in DCM with 0.3% TEA)

Sources & evidence

ORD record: ord-89760c4001bb4ad5b5d0ac62361bb5d5
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273051B2

Reaction notes

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