Nitrogen → HCID 59402315, compound

HRID 2090400Notes

Reaction equation

HRID 2090400 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[C:3]1[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].Br[C:27]1[CH:36]=[C:35]2[C:30]([CH2:31][CH:32]([CH3:51])[N:33]([C:37]3[CH:42]=[C:41]([N:43]4[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]4)[N:40]=[C:39]([NH2:50])[N:38]=3)[CH2:34]2)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].N#N>O1CCOCC1.O.C(OCC)(=O)C.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>[NH2:50][C:39]1[N:38]=[C:37]([N:33]2[CH:32]([CH3:51])[CH2:31][C:30]3[C:35](=[CH:36][C:27]([C:5]4[CH:4]=[C:3]([C:16]([O:18][CH2:19][C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=5)=[O:17])[N:2]([CH3:1])[CH:6]=4)=[CH:28][CH:29]=3)[CH2:34]2)[CH:42]=[C:41]([N:43]2[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]2)[N:40]=1

Participants

9

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 594023174-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amineHCID 59402364Benzyl 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxylate

Product 1

HCID 59402315HCID 59402315, compound

Reagents, catalysts & solvents 4

HCID 178482906HCID 178482906, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of benzyl 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-2-carboxylate (78.5 mg, 0.230 mmol), 4-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (0.080 g, 0.19 mmol) (Peak 1, Example 49, Step 7), dichloro(bis{di-tert-butyl[4-(dimethylamino)phenyl]phosphoranyl})palladium (4.07 mg, 0.00575 mmol), and sodium carbonate (0.0406 g, 0.383 mmol) in 1,4-dioxane (0.88 mL) and water (0.1 mL) was vacuumed and refilled with N2 for 3 times and then stirred at 90° C. overnight. LCMS monitored reaction. After cooling down to r.t., the mixture was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-10%) to afford the desired product. LCMS (M+H)+: m/z=552.1.

Workup

  1. customreaction
  2. temperatureAfter cooling down to r.t.
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-10%)

Sources & evidence

ORD record
ord-fb3bc2e188894826973acef1aea60385
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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