Methanol → 1-[4-fluoro-7-(3-methylpyrazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dione

HRID 1157280Notes

Reaction equation

HRID 1157280 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([F:32])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.C(=O)([O-])[O-].[K+].[K+].[CH3:39][C:40]1[CH:44]=[CH:43][NH:42][N:41]=1.CO>CN1CCCC1=O.[Cu]>[F:32][C:5]1[CH:4]=[N:3][C:2]([N:42]2[CH:43]=[CH:44][C:40]([CH3:39])=[N:41]2)=[C:7]2[NH:8][CH:9]=[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])[C:6]=12

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 595113051-(7-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dioneHCID 178428694HCID 178428694, compound

Product 1

HCID 248752561-[4-fluoro-7-(3-methylpyrazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dioneYield 13.8%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 1-(7-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (50 mg, 0.1 mmol), potassium carbonate (13 mg, 0.1 mmol), copper (6.0 mg, 0.1 mmol) and 3-methylpyrazole (32 uL, 0.4 mmol) in N-methylpyrrolidinone (0.5 mL) was heated at 160° C. for 6 h. MeOH (3 mL) was added and the solution was filtered through Celite. Solvent was removed in vacuum and residue was dissolved in DMF and purified using reverse phase prep HPLC to afford 1-(4-fluoro-7-(3-methyl-1H-pyrazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (6.9 mg) as a white solid; 1HNMR (500 MHz, CDCl3) δ 8.46 (d, J=2 Hz, 1H), 8.19 (s, 1H), 8.93 (d, J=2.0 Hz, 1H), 7.55-7.50 (m, 5H), 6.25 (d, J=2.0 Hz, 1H), 3.78 (m, 2H), 3.56 (m, 2H), 3.35 (m, 2H), 3.25 (m, 2H), 2.36 (s, 3H). LCMS: m/e 501 (M+H)+, ret time 2.34 min (method 2) and 1-(4-fluoro-7-(5-methyl-1H-pyrazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (13.7 mg); 1HNMR (500 MHz, CDCl3) δ 8.25 (m, 1H), 8.08 (bs, 1H), 7.65 (m, 1H), 7.60 (m, 5H), 6.27 (m, 1H), 3.87 (m, 2H), 3.66 (m, 2H), 3.46 (m, 2H), 3.36 (m, 2H), 2.83 (s, 3H). LCMS: m/e 501 (M+H)+, ret time 2.34 min (method 2).

Workup

  1. filtrationthe solution was filtered through Celite
  2. customSolvent was removed in vacuum and residue
  3. dissolutionwas dissolved in DMF
  4. custompurified

Sources & evidence

ORD record
ord-11e6d26bba044836a3b8127c2e31656c
Source dataset
uspto-grants-2010_10
Patent number
US07807671B2

Reaction notes

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