N,N,N',N'-Tetramethylethylenediamine → HCID 46701122, compound

HRID 2090285Notes

Reaction equation

HRID 2090285 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH2:12][CH2:13][N:14]([C:18]4[CH:23]=[C:22]([N:24]5[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]5)[N:21]=[C:20]([NH2:31])[N:19]=4)[CH2:15]3)=[CH:10][CH:9]=2)=[CH:4][C:3]=1[F:32].[CH3:33][N:34](C)CCN(C)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN1CCCC1=O>[NH2:31][C:20]1[N:19]=[C:18]([N:14]2[CH2:13][CH2:12][C:11]3[C:16](=[CH:17][C:8]([C:5]4[CH:4]=[C:3]([F:32])[C:2]([C:33]#[N:34])=[N:7][CH:6]=4)=[CH:9][CH:10]=3)[CH2:15]2)[CH:23]=[C:22]([N:24]2[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]2)[N:21]=1

Participants

7

Reactant 3

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 46701121HCID 46701121, compound

Product 1

HCID 46701122HCID 46701122, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

4-[7-(6-chloro-5-fluoropyridin-3-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (186 mg, 0.410 mmol, Example 6), Zinc cyanide (57 mg, 0.48 mmol), N,N,N′,N′-tetramethylethylenediamine (86 μL, 0.57 mmol), tris(dibenzylideneacetone)dipalladium(0) (16 mg, 0.018 mmol, Alfa Aesar Cat. No. 12760) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (30 mg, 0.053 mmol) (Aldrich, Cat. No. 526460) were added successively to N-Methylpyrrolidinone (5 mL) in a microwave tube. The tube was sealed and degassed with nitrogen and heated at 160° C. overnight. The reaction mixture was cooled to r.t. and filtered. The filtration was diluted with MeOH and purified by RP-HPLC (pH=10) to afford the desired compound. LCMS (M+H)+: m/z=445.3.

Workup

  1. customThe tube was sealed
  2. customdegassed with nitrogen
  3. temperatureThe reaction mixture was cooled to r.t.
  4. filtrationfiltered
  5. filtrationThe filtration
  6. additionwas diluted with MeOH
  7. custompurified by RP-HPLC (pH=10)

Sources & evidence

ORD record
ord-11f1ab7b861e467daa823fe04ea2ca83
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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