Dichloromethane → HCID 59402271, compound

HRID 2090495Notes

Reaction equation

HRID 2090495 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([CH3:26])[N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH:40]=2)O1.ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[NH2:25][C:14]1[N:13]=[C:12]([N:8]2[CH:7]([CH3:26])[CH2:6][C:5]3[C:10](=[CH:11][C:2]([C:35]4[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=4)=[CH:3][CH:4]=3)[CH2:9]2)[CH:17]=[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]2)[N:15]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 594023174-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

Product 1

HCID 59402271HCID 59402271, compoundYield 59.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(7-bromo-3-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (0.350 g, 0.839 mmol) (Peak 1, Example 49, Step 7), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (0.311 g, 1.01 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (41.1 mg, 0.0503 mmol), potassium carbonate (0.464 g, 3.35 mmol) in 1,4-dioxane (5.0 mL) and water (2.5 mL) was degassed and recharged with nitrogen three times, and heated at 120° C. for 2 h. The reaction was diluted with ethyl acetate and then washed with water and brine, dried over NaSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column eluted with methanol in DCM (0-10%) to afford the desired product (260 mg, 59.7%). LCMS (M+H)+: m/z=520.4.

Workup

  1. customwas degassed
  2. additionThe reaction was diluted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over NaSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on a silica gel column
  8. washeluted with methanol in DCM (0-10%)

Sources & evidence

ORD record
ord-8c140f1380b84860b387f80186618899
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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