Trifluoroacetic acid → 3-[3-({[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-methyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid amide

HRID 1625446Notes

Reaction equation

HRID 1625446 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([NH:14][CH2:15][C:16]2[CH:17]=[C:18]([C:22]3[C:30]4[C:25](=[N:26][CH:27]=[C:28]([C:31]([OH:33])=O)[CH:29]=4)[NH:24][CH:23]=3)[CH:19]=[CH:20][CH:21]=2)=[O:13])[C:7]1=[O:34].[Cl-].[NH4+].F[P-](F)(F)(F)(F)F.C[N+:49](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.FC(F)(F)C(O)=O>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:35]=[CH:36][C:37]=1[F:38])[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([NH:14][CH2:15][C:16]2[CH:17]=[C:18]([C:22]3[C:30]4[C:25](=[N:26][CH:27]=[C:28]([C:31]([NH2:49])=[O:33])[CH:29]=4)[NH:24][CH:23]=3)[CH:19]=[CH:20][CH:21]=2)=[O:13])[C:7]1=[O:34]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 593624353-[3-({[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-methyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid

Product 1

HCID 593625603-[3-({[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-methyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a vial was dissolved 3-[3-({[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-methyl)-phenyl]-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (53 mg, 0.00010 mol) and ammonium chloride (15 mg, 0.00028 mol, Aldrich) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (58 mg, 0.00015 mol, Applied Biosystems) in N,N-dimethylformamide (1.0 mL, Acros). To this was added N,N-diisopropylethylamine (89 uL, 0.00051 mol, Aldrich) and the reaction was stirred at room temperature for 2 hours. The reaction was neutralized with trifluoroacetic acid (100 uL) and purified directly by preparative HPLC to yield the title compound in 30.2 mg (47%) yield. 1H NMR (400 MHz, CDCl3-MeOH-d4) d ppm 9.158 (m, 1H) 8.849 (m, 1H) 8.378 (m, 1H) 7.679 (m, 1H) 7.601-7.477 (m, 2H) 7.435-7.289 (m, 2H) 7.066-6.868 (m, 4H) 6.396 (m, 1H) 5.035 (m, 2H), 4.561 (m, 2H); MS m/z=514.29 M+H.

Workup

  1. custompurified directly by preparative HPLC

Sources & evidence

ORD record
ord-91a6a41b0b8447689a554cd950003779
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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