N,N,N',N'-Tetramethylethylenediamine → HCID 66801722, compound

HRID 2366302Notes

Reaction equation

HRID 2366302 reaction equation
Br[C:2]1[C:3]2[N:18]=[C:17]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:26])[S:16][C:4]=2[C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11][N:10]=2)=[N:6][CH:7]=1.[CH3:27][N:28](CCN(C)C)C>[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].CN(C=O)C>[Cl:26][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]([F:25])[C:19]=1[C:17]1[S:16][C:4]2[C:5]([NH:8][C:9]3[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11][N:10]=3)=[N:6][CH:7]=[C:2]([C:27]#[N:28])[C:3]=2[N:18]=1

Participants

7

Reactant 2

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 56952518HCID 56952518, compound

Product 1

HCID 66801722HCID 66801722, compoundYield 47.9%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 7-bromo-2-(2-chloro-6-fluoro-phenyl)-N-(6-methylpyrimidin-4-yl)thiazolo[5,4-c]pyridin-4-amine (0.15 mmol, 69 mg), Zn(CN)2 (0.30 mmol, 36 mg), Pd2(dba)3 (0.015 mmol, 13.8 mg), and dppf (0.030 mmol, 16.5 mg) in a 10 mL microwave vial was purged with nitrogen for 5 min. DMF (3 mL) and TMEDA (0.03 mmol; 3.6 mg) were added. The vial was sealed and heated at 140° C. in a microwave reactor for 20 min. The reaction mixture was filtered through celite, washed with EtOAc. Filtrate was concentrated to give a crude product which was purified by reverse phase HPLC to give the title compound as an off-white solid (5.7 mg, 9.6% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 8.89 (s, 1H), 8.74 (s, 1H), 7.75 (td, J=8.3, 6.2 Hz, 1H), 7.68 (s, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.54 (t, J=8.9 Hz, 1H), 2.43 (s, 3H). LCMS (Method B): RT=4.33 min, m/z 397.1 [M+H+].

Workup

  1. customwas purged with nitrogen for 5 min
  2. customThe vial was sealed
  3. filtrationThe reaction mixture was filtered through celite
  4. washwashed with EtOAc
  5. concentrationFiltrate was concentrated
  6. customto give a crude product which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-bddfd6223e594b9cb0733eb2e41bdd19
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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