N-bromobutanimide → 7-cyano-1-(3-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester

HRID 642540Notes

Reaction equation

HRID 642540 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:25])=[C:8]2[C:14](Br)=[C:13](Br)[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[C:9]2=[CH:10][N:11]=1)=[O:5])[CH3:2].C1C(=O)[N:30](Br)[C:28](=O)C1.C([Cu])#N.CN1C(=O)CCC1.C([O-])=O.[NH4+]>CC#N.[Pd].CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:25])=[C:8]2[CH:14]=[CH:13][N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[C:9]2=[C:10]([C:28]#[N:30])[N:11]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 67184N-bromobutanimideHCID 2723923Ammonium formateHCID 684286622,3-dibromo-1-(3-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl esterHCID 178480183HCID 178480183, compound

Product 1

HCID 684290287-cyano-1-(3-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared in analogy to that of Example 133(a) from 2,3-dibromo-1-(3-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester and NBS in MeCN to give tribromo intermediate; which was subjected to a cyanation condition CuCN/NMP similar to that of Example 105(a) to give the C-7 CN intermediate; which was further subjected to a reductive debromination condition (ammonium formate, Pd/C in refluxing EtOAc) similar to that of Example 6(a) to give the desired title compound. The title compound, ESI MS (m/z): 340 (M+H)+.

Workup

  1. customto give tribromo intermediate
  2. customto give the C-7 CN intermediate

Sources & evidence

ORD record
ord-511206ca86794aba8d5a829df66a0808
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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