Diisopropylethylamine → 6-[2-[4-methoxy-7-(3-methyl-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-oxo-acetyl]-2-oxo-1-phenyl-7,8-dihydro-5H-1,6-naphthyridine-3-carbonitrile

HRID 885071Notes

Reaction equation

HRID 885071 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.[O:23]=[C:24]1[C:33]([C:34]#[N:35])=[CH:32][C:31]2[CH2:30][NH:29][CH2:28][CH2:27][C:26]=2[N:25]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CCOC(C)=O>[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:29]3[CH2:28][CH2:27][C:26]4[N:25]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[C:24](=[O:23])[C:33]([C:34]#[N:35])=[CH:32][C:31]=4[CH2:30]3)=[O:21])[C:4]=12

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 580260402-Oxo-1-phenyl-1,2,5,6,7,8-hexahydro-1,6-naphthyridine-3-carbonitrileHCID 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 1

HCID 445556026-[2-[4-methoxy-7-(3-methyl-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-oxo-acetyl]-2-oxo-1-phenyl-7,8-dihydro-5H-1,6-naphthyridine-3-carbonitrileYield 4.42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution 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 (70 mg, 0.232 mmol), 2-oxo-1-phenyl-1,2,5,6,7,8-hexahydro-1,6-naphthyridine-3-carbonitrile (58.4 mg, 0.232 mmol) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (90 mg, 0.279 mmol) in DMF (2 mL) was added N,N-diisopropylethylamine (0.406 mL, 2.324 mmol). The mixture was stirred at room temperature for 4 hours, and diluted with EtOAc (100 mL) and washed with 5% of NaHCO3 (20 mL), and brine (20 mL). The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified by prep. HPLC and silica gel column (using EtOAc) to give 6-(2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetyl)-2-oxo-1-phenyl-1,2,5,6,7,8-hexahydro-1,6-naphthyridine-3-carbonitrile (6.1 mg, 10.27 μmol, 4.42% yield). LCMS: m/z 535.09 (M+H)+, 1.65 min (method 7). 1H NMR (500 MHz, chloroform-d) δ ppm 11.07 (s, 1H) 9.05-9.12 (m, 1H) 8.18-8.27 (m, 1H) 7.45-7.78 (m, 5H) 7.14-7.21 (m, 2H) 4.50-4.73 (m, 2H) 3.95-4.04 (m, 3H) 3.64-3.90 (m, 2H) 2.53-2.57 (m, 3H) 2.42-2.50 (m, 2H).

Workup

  1. washwashed with 5% of NaHCO3 (20 mL), and brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by prep

Sources & evidence

ORD record
ord-ddd63eb0d7b044b9bbb0a6aeac628957
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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