Sodium Carbonate → 5-(1-(2,4-difluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)pyrimidin-4-amine

HRID 1186807Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]2=[N:14][CH:15]=[CH:16][C:17](B(O)O)=[C:12]2[CH:11]=[N:10]1.Br[C:22]1[C:23]([NH2:28])=[N:24][CH:25]=[N:26][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCO.COCCOC.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]2=[N:14][CH:15]=[CH:16][C:17]([C:22]3[C:23]([NH2:28])=[N:24][CH:25]=[N:26][CH:27]=3)=[C:12]2[CH:11]=[N:10]1

Participants

Conditions

Temperature: 110 °C

Procedure

Example 67 was prepared according to the general procedure in Example 1, except heating at 110° C. for 4.5 h, and using the following materials: Intermediate 63A (308 mg, 1.120 mmol), 5-bromopyrimidin-4-amine (297 mg, 1.707 mmol), sodium carbonate (484 mg, 4.57 mmol), EtOH:DME:H2O (1.2:2.5:1.0 ratio) (5.0 mL) and tetrakis(triphenylphosphine) palladium(0) (81 mg, 0.07 mmol). Example 67 was isolated as a white solid (124.2 mg, 32.3%). Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 15% Solvent B to 80% Solvent B over 12 min, ret. T=6.0 min. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.65 (1 H, d, J=4.88 Hz), 8.51 (1 H, s), 8.37 (1 H, s), 8.28 (1 H, s), 7.77 (1 H, td, J=8.70, 6.10 Hz), 7.60-7.70 (1 H, m), 7.31-7.45 (2 H, m), 6.98 (2 H, br. s.). LC/MS (Condition B): ret. T=1.99 min, (M+H)+ 325.04. Analytical HPLC: (Condition A): >99%, ret. T=15.36 min, (Condition B): >99%, ret. T=16.81 min, (Condition C): >99%, ret. T=5.47 min, (Condition D): >99%, ret. T=5.81 min.

Workup

customExample 67 was prepared

Sources & evidence

ORD record: ord-e93d015ebb804dc59353ec61950acafa
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673922B2

Reaction notes

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