Dimethylformamide → HCID 70817593, compound

HRID 82120Notes

Reaction equation

HRID 82120 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20](=[O:29])[CH2:21][C:22]4[CH:27]=[CH:26][C:25](Br)=[CH:24][N:23]=4)[CH:16]=[N:17][CH:18]=3)=[O:12])=[CH:9][N:8]([C:30]([CH3:34])([CH3:33])[CH2:31][OH:32])[C:6]=2[N:7]=1.[CH3:35][N:36](C=O)C>CCOC(C)=O.[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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([C:11]([C:13]3[CH:14]=[C:15]([NH:19][C:20](=[O:29])[CH2:21][C:22]4[CH:27]=[CH:26][C:25]([C:35]#[N:36])=[CH:24][N:23]=4)[CH:16]=[N:17][CH:18]=3)=[O:12])=[CH:9][N:8]([C:30]([CH3:34])([CH3:33])[CH2:31][OH:32])[C:6]=2[N:7]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 70817529N-(5-{[2-amino-7-(1-hydroxy-2-methylpropan-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]carbonyl}pyridin-3-yl)-2-(5-bromopyridin-2-yl)acetamide

Product 1

HCID 70817593HCID 70817593, compoundYield 31%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-{5-[2-Amino-7-(2-hydroxy-1,1-dimethyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl]-pyridin-3-yl}-2-(5-bromo-pyridin-2-yl)-acetamide (Example 316, 75 mg, 0.143 mmol) in DMF (2 mL) was added Zn(CN)2 (25 mg, 0.215 mmol) and the reaction mixture was degassed with argon for 10 minutes. Pd2 (dba)3 (3 mg, 0.002 mmol) and 1,1′-bis(diphenylphosphino)ferrocene 6 mg, 0.011 mmol) were then added and the resultant reaction mixture was heated at 100° C. for 40 minutes under microwave irradiation. The reaction mixture was diluted with EtOAc (20 mL) and washed with water (2×10 mL) and brine (10 mL). The organic layer was dried (Na2SO4) and evaporated in vacuo. The crude material was purified by preparative TLC (7% MeOH in DCM) to afford the title compound as yellow solid in 31% yield, 21 mg.

Workup

  1. customthe reaction mixture was degassed with argon for 10 minutes
  2. customthe resultant reaction mixture
  3. washwashed with water (2×10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe crude material was purified by preparative TLC (7% MeOH in DCM)

Sources & evidence

ORD record
ord-ef203eabdfa94ff1bb5670debdc0ade4
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

Loading…