Dimethylformamide → HCID 67340174, compound

HRID 2092303Notes

Reaction equation

HRID 2092303 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[C:14]([NH:20][C:21]4[C:26]([C:27]5[CH:32]=[CH:31][N:30]=[CH:29][N:28]=5)=[CH:25][CH:24]=[CH:23][N:22]=4)[C:13]=3[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.CN(C=O)C.C(N(CC)CC)C.[CH3:45][Si:46]([C:49]#[CH:50])([CH3:48])[CH3:47]>O.ClCCl.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:19][C:15]1[CH:16]=[CH:17][C:18]2[C:9]([NH:8][C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:50]#[C:49][Si:46]([CH3:48])([CH3:47])[CH3:45])[CH:3]=3)=[N:10][CH:11]=[CH:12][C:13]=2[C:14]=1[NH:20][C:21]1[C:26]([C:27]2[CH:32]=[CH:31][N:30]=[CH:29][N:28]=2)=[CH:25][CH:24]=[CH:23][N:22]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 67338500HCID 67338500, compound

Product 1

HCID 67340174HCID 67340174, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Dissolved N1-(3-bromophenyl)-6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)isoquinoline-1,5-diamine (0.1125 g, 0.233 mmol) in DMF (0.427 ml, 5.84 mmol) and triethylamine (0.162 ml, 1.16 mmol). Added trimethylsilylacetylene (0.0987 ml, 0.698 mmol) followed by copper (I) iodide (0.00887 g, 0.0465 mmol) and bis(triphenylphosphine)palladium (II) chloride (0.0163 g, 0.0233 mmol). Sealed vessel and stirred reaction mixture at 70° C. After 48 hours, the reaction mixture was diluted with 100 mL water and 100 mL dichloromethane. The layers were separated and the organics washed with 2× water and 2× brine. The organics were dried over sodium sulfate, concentrated in vacuo and purified by column chromatography (20-80% EtOAc/hexanes). The combined fractions of the main peak were concentrated in vacuo to afford 6-methyl-N5-(3-(pyrimidin-4-yl)pyridin-2-yl)-N1-(3-(2-(trimethylsilyl)ethynyl)phenyl)isoquinoline-1,5-diamine as a crystalline solid. MS (M+H)+ 501.2.

Workup

  1. customSealed vessel
  2. customreaction mixture at 70° C
  3. customThe layers were separated
  4. washthe organics washed with 2× water and 2× brine
  5. dry with materialThe organics were dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (20-80% EtOAc/hexanes)
  8. concentrationThe combined fractions of the main peak were concentrated in vacuo

Sources & evidence

ORD record
ord-4e56b8eac834442b8b5b62b8c807cc78
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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