Trifluoroacetic acid → Trifluoroacetic acid

HRID 885078Notes

Reaction equation

HRID 885078 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([OH:21])=O)[C:4]=12.[C:23]1([C:29]2[N:38]=[CH:37][CH:36]=[C:35]3[C:30]=2[CH2:31][CH2:32][NH:33][CH2:34]3)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([N:33]3[CH2:32][CH2:31][C:30]4[C:35](=[CH:36][CH:37]=[N:38][C:29]=4[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:34]3)=[O:21])[C:4]=12.[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58026061HCID 58026061, compoundHCID 596815922-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid

Product 2

HCID 6422Trifluoroacetic acidYield 76%HCID 58026048HCID 58026048, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.124 g, 0.413 mmol) and 5-phenyl-1,2,3,4-tetrahydro-2,6-naphthyridine, TFA (0.147 g, 0.454 mmol) in DMF (5 mL) was added Hunig's Base (0.5 mL, 2.86 mmol) followed by TBTU (0.172 g, 0.537 mmol). The solution was stirred at rt for 5 h and quenched with 5 mL of water. The solvent was removed under reduced pressure and the residue dissolved in DMF and passed through a plug of glass wool. The DMF solution was purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure. The residue was further purified by BIOTAGE® flash chromatography using a 0-5% MeOH in dichloromethane gradient. The expected product, 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-phenyl-3,4-dihydro-2,6-naphthyridin-2(1H)-yl)ethane-1,2-dione, TFA (0.192 g, 0.314 mmol, 76% yield), was isolated as an off-white solid. LC/MS: m/z 494.12 (M+H)+, 0.878 min (method 6). 1H NMR (500 MHz, DMSO-d6) δ ppm 12.40-12.47 (m, 1H) 9.24 (s, 1H) 8.47-8.58 (m, 1H) 8.25-8.32 (m, 1H) 7.87 (s, 1H) 7.30-7.63 (m, 6H) 4.75-4.96 (m, 2H) 3.59-3.88 (m, 5H) 2.78-2.99 (m, 2H) 2.48-2.52 (m, 3H).

Workup

  1. customquenched with 5 mL of water
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue dissolved in DMF
  4. customThe DMF solution was purified by prep HPLC
  5. additionThe fractions containing the expected product
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was further purified by BIOTAGE® flash chromatography

Sources & evidence

ORD record
ord-070b404f0286420baaf15aed1aa63ca7
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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