Dimethylformamide → 2(5-cyanopyridin-2-yl)-N-(4-{[1-(propan-2-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl]carbonyl}pyridin-2-yl)acetamide

HRID 1753003Notes

Reaction equation

HRID 1753003 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]([C:20]3[C:24]4[CH:25]=[N:26][CH:27]=[CH:28][C:23]=4[N:22]([CH:29]([CH3:31])[CH3:30])[CH:21]=3)=[O:19])[CH:15]=[CH:14][N:13]=2)=[O:10])=[N:6][CH:7]=1.[CH3:32][N:33](C=O)C>C(OCC)(=O)C.[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].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]>[C:32]([C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]([C:20]3[C:24]4[CH:25]=[N:26][CH:27]=[CH:28][C:23]=4[N:22]([CH:29]([CH3:31])[CH3:30])[CH:21]=3)=[O:19])[CH:15]=[CH:14][N:13]=2)=[O:10])=[N:6][CH:7]=1)#[N:33]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 900941972-(5-bromopyridin-2-yl)-N-(4-{[1-(propan-2-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl]carbonyl}pyridin-2-yl)acetamide

Product 1

HCID 1183412202(5-cyanopyridin-2-yl)-N-(4-{[1-(propan-2-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl]carbonyl}pyridin-2-yl)acetamide

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

A mixture of 2-(5-bromopyridin-2-yl)-N-(4-{[1-(propan-2-yl)-1H-pyrrolo[3,2-c]pyridin-3-yl]carbonyl}pyridin-2-yl)acetamide (Example 237, 40 mg, 0.083 mmol), zinc cyanide (29 mg, 0.251 mmol), Pd2(dba)3 (3 mg, 0.003 mmol) and DPPF (7.5 mg, 0.013 mmol) in DMF (1 mL) was heated to 100° C. under microwave irradiation for 25 minutes. The reaction was cooled and diluted with ethyl acetate. The organic layer was collected, washed with water, brine, dried over sodium sulphate and concentrated in vacuo. The residue was purified using preparative TLC eluting with 5% MeOH in DCM to afford the LCMS (5 minute run) Rt=2.78 minutes MS m/z 425 [M+H]+

Workup

  1. temperatureThe reaction was cooled
  2. customThe organic layer was collected
  3. washwashed with water, brine
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified
  7. washeluting with 5% MeOH in DCM
  8. customto afford the LCMS (5 minute run) Rt=2.78 minutes MS m/z 425

Sources & evidence

ORD record
ord-f3e8403907884c2280ecf84d8503ea8d
Source dataset
uspto-grants-2015_10
Patent number
US09163021B2

Reaction notes

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