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

HRID 1157748Notes

Reaction equation

HRID 1157748 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+].[NH2:39][C:40]1[CH:44]=[CH:43][NH:42][N:41]=1>CN1CCCC1=O.[Cu]>[NH2:39][C:40]1[CH:44]=[CH:43][N:42]([C:2]2[N:3]=[CH:4][C:5]([F:32])=[C:6]3[C:10]([C:11](=[O:31])[C:12]([N:14]4[CH2:15][CH2:16][N:17]([C:20]5[N:24]([C:25]6[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=6)[N:23]=[N:22][N:21]=5)[CH2:18][CH2:19]4)=[O:13])=[CH:9][NH:8][C:7]=23)[N:41]=1

Participants

6

Reactant 3

HCID 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 178418806HCID 178418806, compound

Product 1

HCID 248752931-[7-(3-aminopyrazol-1-yl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dioneYield 15.9%

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 (100 mg, 0.2 mmol), potassium carbonate (26 mg, 0.2 mmol), copper (13 mg, 0.2 mmol) and 3-aminopyrazole (100 uL, 1 mmol) in N-methylpyrrolidinone (0.5 mL) was heated at 160° C. for 5 h. Solvent was removed in vacuum and residue was dissolved in DMF and purified using reverse phase prep HPLC to afford 1-(7-(3-amino-1H-pyrazol-1-yl)-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 (15.9 mg) as a pale yellow solid; 1HNMR (500 MHz, DMSO) δ 8.34 (d, J=2.0 Hz, 1H), 8.29 (d, J=1.5 Hz, 1H), 8.03 (s, 1H), 7.70-7.58 (m, 5H), 5.92 (d, J=2.5 Hz, 1H), 5.25 (m, 2H), 3.71 (m, 2H), 3.47 (m, 2H), 3.32 (m, 2H), 3.16 (m, 2H). LCMS: m/e 502 (M+H)+, ret time 1.26 min (method 3); and 1-(7-(5-amino-1H-pyrazol-1-yl)-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 (8.8 mg) as a pale yellow solid; 1HNMR (500 MHz, CDCl3) δ 8.21 (m, 1H), 8.11 (bs, 1H), 7.60 (m, 6H), 6.94 (m, 2H), 5.52 (m, 1H), 3.71 (m, 2H), 3.47 (m, 2H), 3.31 (m, 2H), 3.16 (m, 2H); LCMS: m/e 502 (M+H)+, ret time 1.26 min (method 3).

Workup

  1. customSolvent was removed in vacuum and residue
  2. dissolutionwas dissolved in DMF
  3. custompurified

Sources & evidence

ORD record
ord-14ee62a1178745d1b09e1d507c04513c
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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