Nitrogen → 4-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(1H-pyrazol-3-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine

HRID 2090389Notes

Reaction equation

[NH:1]1[CH:5]=[CH:4][C:3](B(O)O)=[N:2]1.Br[C:10]1[CH:19]=[C:18]2[C:13]([CH2:14][CH:15]([CH3:34])[N:16]([C:20]3[CH:25]=[C:24]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[N:23]=[C:22]([NH2:33])[N:21]=3)[CH2:17]2)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+].N#N>O1CCOCC1.O.Cl[Pd](Cl)(P(C(C)(C)C)(C(C)(C)C)C1C=CC(N(C)C)=CC=1)P(C1C=CC(N(C)C)=CC=1)(C(C)(C)C)C(C)(C)C>[CH3:32][N:29]1[CH2:28][CH2:27][N:26]([C:24]2[CH:25]=[C:20]([N:16]3[CH:15]([CH3:34])[CH2:14][C:13]4[C:18](=[CH:19][C:10]([C:3]5[CH:4]=[CH:5][NH:1][N:2]=5)=[CH:11][CH:12]=4)[CH2:17]3)[N:21]=[C:22]([NH2:33])[N:23]=2)[CH2:31][CH2:30]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 1H-pyrazol-3-ylboronic acid (64.3 mg, 0.575 mmol, Frontier Scientific, Cat. No. P1638), 4-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (0.20 g, 0.48 mmol) (Peak 2, Example 49, Step 7), dichloro(bis{di-tert-butyl[4-(dimethylamino)phenyl]phosphoranyl})palladium (10.2 mg, 0.0144 mmol), and sodium carbonate (0.102 g, 0.958 mmol) in 1,4-dioxane (2.2 mL) and water (0.3 mL) was vacuumed and refilled with N2 for 3 times and then stirred at 90° C. overnight. The mixture was purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=405.2.

Workup

customThe mixture was purified by RP-HPLC (pH=10)

Sources & evidence

ORD record: ord-38b53afe82f54f8982d2d4b01e6fb2be
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436008B2

Reaction notes

Loading…